|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2645-2657
REVIEW ARTICLE
Integrin Signaling: The Platelet Paradigm
By
Sanford J. Shattil,
Hirokazu Kashiwagi, and
Nisar Pampori
From the Departments of Vascular Biology and Molecular and
Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
 |
INTRODUCTION |
ADHESION IS REQUIRED for cell
growth, differentiation, survival, and function. Nowhere is this more
evident than in the response to tissue injury, where vascular damage
triggers reparative processes, such as hemostasis, inflammation, and
wound healing. These processes depend on a coordinated series of cell
adhesion and migration events by platelets, leukocytes, and vascular
cells for their successful execution.1 Cell adhesion is
mediated by a structurally diverse group of plasma membrane receptors,
each exhibiting specialized ligand-binding properties that are needed
for specific tasks in the injury response. For example, when blood
flows through a damaged blood vessel, leukocytes slow down and roll on
the endothelial surface as a consequence of the interaction of
appropriate sialyl Lewis X-rich membrane glycoproteins on the
leukocytes with selectins on the endothelial cells.2,3
Platelets also roll under conditions of high shear on perturbed
endothelium4 as well as on denuded vascular surfaces, in
the latter case through interactions of the platelet glycoprotein (GP)
Ib-V-IX complex with von Willebrand factor (vWF) in the subendothelial
matrix.5 Once the rolling process has slowed down these
blood cells, they come to an abrupt stop at the right place through
regulated interactions between integrin adhesion receptors and either
counter-receptors on endothelial cells or adhesive proteins in the
matrix.2,5 Integrins also mediate responses necessary for
eventual completion of the injury response, including leukocyte
transmigration and platelet aggregation.2,6
Although adhesion receptors rightfully deserve this moniker, any
implication that they are simply cellular velcro is incorrect. Most, if
not all, adhesion receptors engage in a dialogue with the extracellular
and intracellular milieus. Integrins are a case in point. Cells often
regulate ligand binding to integrins through a process known as
inside-out signaling or integrin activation. Furthermore, once
integrins have become occupied and clustered by their ligands, they can
transmit information into cells. These outside-in signals collaborate
with signals originating from growth factor receptors and other plasma
membrane receptors to regulate a host of anchorage-dependent cellular
functions. One of the best studied cases of integrin signaling involves
 IIb 3, an integrin of particular
significance to hematologists because it is required for aggregation
and adhesive spreading of platelets during hemostasis (Fig 1). The purpose of this review is to describe the
platelet paradigm of integrin signaling and to emphasize the advances
and gaps in our understanding of this process and place it into
clinical perspective. We have tried to cite authoritative reviews
whenever possible to provide interested readers with additional sources of primary references. Several excellent general reviews of
integrins7-12 and platelet biochemistry13,14
are available.
View larger version (49K):
[in this window]
[in a new window]
| Fig 1.
Integrin signaling in hemostasis. Platelet adhesion to
the damaged vessel wall is initiated by platelet rolling, an
integrin-independent event mediated by binding of GP Ib-V-X
to vWF (left panel). Subsequent stationary adhesion and primary
platelet aggregation require inside-out signaling through and
ligand binding to IIb3 (center panel). Full platelet spreading, aggregation, and effective hemostatic plug
formation also require outside-in signaling through
IIb3 (right panel).
|
|
| |
WHAT IS INTEGRIN SIGNALING? |
IIb3 consists of a two-chain subunit
bound noncovalently to a single-chain subunit. Each subunit spans
the platelet membrane once. The N-terminus and most of the remainder of
each subunit are extracellular, and the membrane-spanning domain is connected to a short C-terminal cytoplasmic tail consisting of 20 amino
acid residues in IIb and 47 residues in
3. Electron microscopy of heterodimers shows an
N-terminal globular head connected to two C-terminal
stalks.15,16 Although the atomic structure of
IIb3 is not known, biochemical, genetic,
and molecular modeling studies indicate that ligand binding is
primarily a function of the globular heads.17 Because
ligand binding is regulated by signals from within the platelet and
also triggers platelet responses, mechanisms must exist to propagate
information back and forth between the cytoplasmic tails and the
globular heads. This overall process is referred to as integrin
signaling.
A didactic distinction is often made between inside-out and outside-in
signaling. Inside-out signaling denotes those reactions initiated by
the binding of one or more agonists to their plasma membrane receptors,
leading to the conversion of IIb3 from a low-affinity/avidity receptor to a high-affinity/avidity receptor. This
conversion has profound consequences in that it determines whether
IIb3 can engage soluble adhesive ligands,
such as fibrinogen and vWF, which contain a classical integrin
recognition sequence, Arg-Gly-Asp. These multivalent ligands can
function as bridges between receptors on adjacent platelets, thus
allowing platelet aggregation to proceed.18 Because
IIb3 can diffuse laterally within the
plasma membrane, inside-out signaling can have two distinct components
that are often difficult to distinguish in practice: (1) affinity
modulation, which implies a structural change intrinsic to the
heterodimer that results in a greater strength of ligand binding; and
(2) avidity modulation, which implies a change in the functional
affinity of the interaction between receptor and ligand due
to chelate or rebinding effects.19 One
plausible way that the latter could occur is through integrin clustering within the plane of the plasma membrane
(Fig 2).
View larger version (61K):
[in this window]
[in a new window]
| Fig 2.
What is integrin signaling? In this cartoon of the
platelet membrane interface, arrows labeled 1a and 1b denote inside-out signaling pathways and arrow 2 denotes outside-in signaling
pathways. Inside-out signaling increases the affinity (1a)
and avidity (1b) of IIb3 for ligands such
as fibrinogen. Affinity modulation is depicted hypothetically here as a
signal-induced rotation of the 3 subunit to generate and
unmask fibrinogen binding sites in the extracellular domains of
IIb3. Outside-in signaling triggers a
number of postligand binding events and these require cooperative signaling between IIb3 and agonist
receptors (hashed arrow).
|
|
Outside-in signaling denotes reactions initiated by integrin ligation
and clustering, and these must be coordinated with signals emanating
from other plasma membrane receptors (eg, growth factor, cytokine, and
G-protein-linked receptors).10,20,21 Integrin signals help
to regulate a host of postligand binding events, the particular pattern
varying with the cell and the integrin. Postligand binding events
regulated by IIb3 in platelets include the stabilization of large platelet aggregates, platelet spreading, granule secretion, clot retraction, and possibly platelet procoagulant activity.22
| |
INSIDE-OUT SIGNALING IN PLATELETS |
Resting platelets contain about 80,000 surface copies of
IIb3, with additional pools of
IIb3 in the membranes of -storage granules and the open-canalicular system.23 The binding of
soluble ligands to IIb3 can be detected
within seconds of platelet activation, and it reaches a steady-state
within minutes.18,24 Although ligand binding is at first
reversible, it becomes progressively irreversible.22
Purified IIb3 can bind fibrinogen with a
stoichiometry up to a 1:1, but the stoichiometry may be lower in
platelets. Although ligand-binding to surface-expressed
IIb3 is essential for initial, primary
platelet aggregation, the internal pools of
IIb3 can become exposed after cell
activation and participate in the secondary phase in which larger
platelet aggregates are formed. In fact, the -granule membrane pool
of IIb3 may already be complexed with
fibrinogen stored within these granules.25 Should the
surface pool of receptors on resting platelets become unavailable to
bind ligand, as for example after infusion of a function-blocking
antibody,26 the -granule pool may be able to support
platelet aggregation.27
Affinity versus avidity modulation.
Platelets and other cells use a conformational switch mechanism
(affinity modulation) and receptor clustering (avidity modulation) to
regulate ligand binding to integrins, and the relative contribution of
each varies with the integrin and the cell type.28,29
Ligand binding studies alone cannot usually distinguish between these two mechanisms. Available evidence indicates that the initial, reversible phase of ligand binding to
IIb3 is due to affinity modulation,
whereas the irreversible phase may be due to several factors, including
(1) ligand-induced changes intrinsic to the receptor (perhaps analogous
to those responsible for induced fit between an antibody and
antigen)30,31; (2) receptor clustering32-35;
and (3) receptor internalization.36 In addition,
thrombospondin and other substances released from -granules during
secretion may bind to fibrinogen and/or
IIb3 and stabilize the ligand-receptor interaction.37 An initial conformational switch mechanism
is consistent with the rapid and selective binding of a monovalent, ligand-mimetic antibody Fab fragment to
IIb3 after platelet activation.38 Moreover, fluorescence resonance energy
transfer studies using monoclonal antibodies bound to extracellular
domains of IIb and 3 show that platelet
activation is associated with a change in the relative orientation of
the subunits.39 Electron micrographs of purified
IIb3 have shown that fibrinogen binding to the globular head of the integrin can be triggered by interaction of
a monoclonal antibody with the membrane-proximal stalk of
3.40 This proves that a long-range
conformational change can be propagated along the integrin, a possible
requirement for affinity modulation. It is logical to assume that
IIb3 also clusters into multimers in
response to cytoskeletal changes during platelet activation. A
subpopulation of IIb3 already is linked
to the membrane skeleton in resting platelets, and there is a wholesale
redistribution of this integrin to the F-actin core cytoskeleton during
platelet activation.14 However, major cytoskeletal
rearrangements do not seem necessary for initial high-affinity ligand
binding to IIb3, because inhibitors of
actin polymerization have a minimal effect on reversible ligand
binding, although they do have a more substantial effect on
irreversible binding.34
The structural changes in IIb3
responsible for interconversion between low- and high-affinity states
are not known. One model posits that the signaling reactions triggered
by platelet agonists cause some modification of the integrin
cytoplasmic tails which is then propagated to the extracellular domains
to effect ligand binding (Fig 2). Recent progress has been made in
understanding the kinds of structural changes in the globular head of
IIb3 that may be required. Based on model
building and the functional effects of mutations,
Springer41 has proposed that the N-terminal region of
IIb (and other integrin subunits) conforms to the shape of a -propeller with seven blades oriented radially and pseudosymmetrically around a central axis and parallel to the plasma
membrane. The ligand binding interface would lie on the top surface of
the propeller (Fig 3). Tozer et
al42 have proposed that a second ligand binding site is
located in an N-terminal region of 3 that bears homology
with an I-domain, which is, ironically, a ligand-binding module of
approximately 190 amino acids inserted within certain subunits (but
not IIb). Crystallographic analyses of I domains from
L and M show an / fold consisting
of seven -helices packed against a six-stranded -sheet. At one
end of the -sheet is a cation binding MIDAS motif implicated in
ligand binding (Fig 3).43,44
View larger version (80K):
[in this window]
[in a new window]
| Fig 3.
A model depicting the potential changes in the
extracellular domains of IIb3 that are
required for high-affinity ligand binding. The top left panel shows an
overhead view of the proposed -propeller domain within the
N-terminal segment of IIb,41 and the top
right panel shows the crystal structure of an I-domain,43 a
homologue of which appears to be present in the N-terminal segment of
3.42 Open circles denote divalent cations
and asterisks denote regions presumed to be directly involved in ligand
binding. Thick ribbons are strands of -sheet, and coiled ribbons are
-helices (adapted from Chothia and Jones172 with
permission, from the Annual Review of Biochemistry, Volume 66, ©1997, by Annual Reviews Inc). The bottom panels illustrate
potential changes in these domains as
IIb3 is converted from a resting state
(left panel) to an activated state (right panel). (Adapted from Loftus
and Liddington.45 Adapted and reproduced from The Journal
of Clinical Investigation, 1997, Vol. 99, pp. 2302, by copyright
permission of The American Society for Clinical Investigation.)
|
|
Based on this information, Loftus and Liddington45 have
proposed a model for the conformational switch in
IIb3 that provides a good framework for
further studies. It predicts that, in resting platelets, the
I-domain-like region in 3 is incapable of binding ligand, but it occludes the ligand binding site in
IIb.45 Platelet activation would then induce
ligand binding by (1) causing a conformational change in the
3 I domain to expose its ligand binding site and (2)
changing the orientation of the subunits to unmask the ligand binding
site in IIb (Fig 3). This implies that the receptor may engage discontinuous regions of the ligand, consistent with the fact that each fibrinogen monomer is multivalent with respect to
IIb3. For example, the C-terminus of the
fibrinogen  chain is essential for initial binding of the soluble
ligand to platelet IIb3,46,47
but one or both of the Arg-Gly-Asp sites in the A chain may provide
secondary points of attachment needed for tighter binding. These A
sites may also assume importance when the fibrinogen is immobilized on
a surface or converted to fibrin.48,49
Reactions that initiate and propagate inside-out signaling.
Inside-out signaling involves reactions that (1) initiate and propagate
the flow of information from agonist or antagonist receptors to
integrin proximal effectors and (2) directly effect integrin activation
or deactivation. Currently, only a broad outline of these reactions can
be provided.
Inside-out signaling is triggered by many excitatory agonists, some of
which, including thrombin, ADP, epinephrine, and thromboxane A2, bind to heptahelical receptors coupled to
heterotrimeric () G proteins.13,50-52 In the case
of some of these agonists, one consequence important for inside-out
signaling is activation of phospholipase C by the
activated subunit of Gq, resulting in hydrolysis of
phosphatidylinositol and production of the second messengers,
diacylglycerol and IP3. Mouse platelets that have been
rendered null for Gq undergo shape change but fail to
aggregate in response to thrombin, ADP, or a thromboxane A2
receptor agonist, and the mice exhibit prolonged tail bleeding
times.53 Occupancy of many G-protein-coupled platelet
receptors also leads to rapid activation of nonreceptor protein
tyrosine kinases, including Src, Syk, and Pyk2 (also known as RAFTK or
CAK).54,55 Although the mechanism by which G proteins
couple to tyrosine kinase cascades in platelets has not been
characterized, the net result is tyrosine phosphorylation of a number
of proteins, including phospholipase C ,56
Vav (a guanine nucleotide exchange factor for the Rac GTP-ase), and
cortactin (a cortical actin-binding protein).54,57,58 A
role for tyrosine phosphorylation-dephosphorylation in integrin activation is suggested by observations that tyrosine kinase inhibitors partially block fibrinogen binding and platelet aggregation, whereas inhibitors of protein tyrosine phosphatases trigger platelet
activation.14,54,59 Furthermore, mouse platelets that have
been rendered null for Syk show a modest reduction in fibrinogen
binding in response to ADP and epinephrine.60 Additional
support for a tyrosine phosphorylation-integrin activation connection
comes from studies of three agonist receptors that are not known to be
coupled to G proteins.
The Fc receptor, FcRIIA, contains an immune receptor tyrosine
activation motif (ITAM) in its cytoplasmic tail. When the receptor is
clustered by aggregated Igs, two tyrosines in the ITAM are phosphorylated by a Src family kinase, enabling Syk, which contains tandem SH2 domains, and possibly other proteins with SH2 domains to
bind. This leads to Syk activation and, eventually, platelet aggregation.61,62 Surprisingly, a similar scheme may
underlie platelet aggregation by collagen. Collagen supports platelet
adhesion indirectly by helping to retain vWF in the vessel
wall.63,64 It also supports adhesion directly through
interactions with integrin 21 and GP IV
(CD36).65,66 However, none of these interactions is
sufficient to trigger platelet activation and recent evidence implicates a 62-kD membrane protein, GP VI, in this
process.67 GP VI exists in a complex with FcR, a 14-kD
ITAM-containing signaling subunit.68,69 Collagen or
suitable triple helical collagen-like peptides bind to GP VI,
stimulating tyrosine phosphorylation of FcR, activation of Syk, and
tyrosine phosphorylation and activation of phospholipase
C2.70,71 A similar chain of events is
observed if platelets are incubated with convulxin, a snake venom
protein specific for GP VI,72 or if GP VI is cross-linked
by an antibody.67 Collagen-induced platelet aggregation is
absent in patients deficient in GP VI as well as in mice null for Fc
or Syk.67,73 Interestingly, activation of Syk and
IIb3 is also triggered by platelet
adhesion to vWF, despite the fact that the relevant adhesion receptor, GP Ib-V-IX, does not possess ITAMs.74
Thus, one common feature of most agonists that activate
IIb3 is their ability to induce
(poly)phosphoinositide hydrolysis and formation of IP3 and
diacylglycerol, either through Gq and phospholipase
C or through tyrosine kinases and phospholipase C.51 IP3 stimulates an increase in
cytoplasmic free Ca2+, but this alone is not sufficient to
activate IIb3.75 A
Na+/Ca2+ exchanger may change the sensitivity
of IIb3 to agonists, but it is not clear
how.76 Activation of conventional PKC isoforms by
diacylglycerol (or by phorbol myristate acetate) leads to activation of
IIb3, a response blocked by PKC
inhibitors.77 A prominent PKC substrate in platelets is
pleckstrin, a protein with two PH domains,78 but no
functional link between pleckstrin and
IIb3 has been established.
Parenthetically, MARCKS proteins are prominent PKC substrates in some
cells, and they have been implicated in integrin-dependent spreading of
macrophages.79
Another signaling molecule that has been implicated in integrin
function is phosphatidylinositol 3-kinase (PI 3-kinase), which converts
PtdIns(4)P and PtdIns(4,5)P2 to the
3-phosphorylated phosphoinositides, PtdIns(3,4)P2
and PtdIns(3,4,5)P3, respectively.80,81 Two
isoforms of this enzyme have been described in platelets, p85/p110 and
p110.80,82 The catalytic activity and subcellular localization of the p110 subunit of p85/p110 are regulated through protein-protein interactions of p85, which contains a Bcr homology domain, SH3 domain, two SH2 domains, and proline-rich sequences. Accordingly, this isoform would be expected to be regulated by proteins
that become tyrosine phosphorylated in response to platelet agonists.
Consistent with this idea, PI 3-kinase can be coprecipitated with Src
and Syk from lysates of activated platelets.83,84 The
catalytic activity of p110, which exists in a complex with a 101-kD
protein, is regulated by G protein subunits.80,82
PtdIns(3,4)P2 and PtdIns(3,4,5)P3 are
membrane-embedded and transduce signals, at least in part, by binding
proteins via their specific PH or SH2 domains and recruiting them to
the membrane. Examples include the PH domain-containing proteins, Akt,
a serine-threonine kinase, and TIAM-1, a Rho family guanine nucleotide
exchange protein; or the SH2 domain-containing proteins,
phospholipase C and Src.85 In platelets, thrombin
stimulates a rapid and transient increase in
PtdIns(3,4,5)P3 and a later increase in
PtdIns(3,4)P2. Whereas inhibitors of PI 3-kinase partially
block agonist-induced activation of IIb3
and platelet aggregation,80 it has been suggested that
3-phosphorylated phosphoinositides function more to stabilize fibrinogen binding than to initiate it.86 Furthermore,
accumulation of PtdIns(3,4)P2 is dependent on fibrinogen
binding to IIb3,80 more
consistent with a role for this particular lipid in outside-in signaling. Indeed, PtdIns(3,4)P2 has been implicated in
mediating actin assembly within filopodia and in stimulating a late
phase of pleckstrin phosphorylation in activated
platelets.80,87,88 One possible link between PI 3-kinase,
PKC, and affinity modulation of IIb3 is
the observation that 3-phosphorylated phosphoinositides can
activate certain atypical and novel isoforms of PKC, some of which are
present in platelets.14,85
Members of the Ras superfamily of GTP-ases have also been implicated in
integrin function. Platelets contain several members of the Ras (H-Ras,
Rap1a) and Rho (cdc42, Rac1, RhoA) families and proteins that regulate
their GDP/GTP contents: guanine nucleotide exchange factors, guanine
nucleotide dissociation inhibitors, and GTP-ase activating
proteins.14 Rac1 regulates thrombin-induced actin
polymerization in platelets.89 It has been suggested that RhoA regulates platelet aggregation based on the observation that C3
exoenzyme, an inhibitor of Rho, blocks aggregation responses to
thrombin.90 However, C3 exoenzyme has no effect on affinity modulation of IIb3 or primary platelet
aggregation, although it does block the formation of focal adhesions
and stress fibers during platelet spreading on
fibrinogen.91 Thus, one function of Rho A may be to
regulate cytoskeletal organization and integrin clustering rather than
integrin affinity.92 Expression of activated R-Ras
increases integrin-mediated adhesion in some cells,93 but
its presence in platelets has not been demonstrated. Thrombin stimulation of platelets causes GTP loading of H-Ras in a PKC-dependent manner and of Rap1 in a Ca2+-dependent
manner.94,95 Platelets contain several potential H-Ras
effectors, including PI 3-kinase and Raf-1, and thrombin induces
activation of MAP (ERK2) kinase in platelets, possibly through the
classical H-Ras pathway.96 When overexpressed in CHO cells,
activated H-Ras or Raf-1 can suppress integrin
activation.97 In platelets, the converse is true: the ERK2
response to thrombin is dampened by fibrinogen binding and
aggregation.98
Pathways that inhibit IIb3 are just as
important as those that activate it. Prostaglandin I2
produced by endothelial cells is a potent platelet activation and
aggregation inhibitor that binds to a specific Gs-coupled heptahelical
receptor, thereby activating adenylyl cyclase and cyclic AMP-dependent
protein kinase (PKA). Platelet aggregation is also inhibited by nitric
oxide, which is synthesized by both endothelial cells and platelets and activates soluble guanylyl cyclase (PKG).99 The importance
of the nitric oxide inhibitory pathway in vivo is shown by two brothers with a defect in the bioavailability of nitric oxide, heightened platelet reactivity to agonists, and a history of cerebrovascular events.100 One common substrate of PKA and PKG is VASP, a
50-kD protein that localizes to focal adhesions and regulates actin dynamics.101 The phosphorylation of VASP on specific serine
residues by agents that activate PKA or PKG correlates with inhibition of platelet aggregation.102 However, PKA and PKG are likely
to exert their inhibitory effects on IIb3
at several levels of stimulus-response coupling, implying that more
than one effector of these serine-threonine kinases is
involved.13,102,103 CD39 is an ecto-ADPase on endothelial
cells that may be an important regulator of platelet responses to
ADP.104 Platelets express PDGF -receptors and store PDGF
in their -granules. Incubation of platelets with PDGF dampens
subsequent aggregation responses to excitatory agonists.105
Reactions that effect inside-out signaling.
The conformational switch necessary for ligand binding to
IIb3 could be regulated by intracellular
molecules that bind to the cytoplasmic tails of the integrin or by
integrin-associated membrane proteins. Evidence directly implicating
the cytoplasmic tails in affinity modulation comes from studies of
naturally occurring and experimental integrin mutations, from analyses
of IIb3 function in heterologous
expression systems, and from identification of integrin tail-binding
proteins. In addition, several membrane proteins have been reported to
form complexes with IIb3 or other integrins.
The sequences of the cytoplasmic tails of IIb and
3 are shown in Fig 4. Two
patients with genetic abnormalities in the 3 cytoplasmic
tail provide living examples of the importance of this tail in integrin
signaling. Both exhibit bleeding disorders of mild to moderate severity
due to variant thrombasthenia: despite near-normal levels of
IIb3, their activated platelets bind
neither fibrinogen nor aggregate. One of these individuals exhibits a point mutation in 3 (3
S752P),106 the other exhibits a deletion of the 39 C-terminal residues from the 3 tail
(3  724).107 In each case, the
profound defect in activation of IIb3 can be recapitulated by expressing the recombinant mutant in CHO
cells.107,108 Transfection studies in CHO cells and in a
B-lymphocyte cell line have shown that other mutations in the
cytoplasmic tails also affect IIb3
affinity.109-113 These results can be summarized as follows. Wild-type IIb3 exists in a
default low-affinity state in these cells, but two different classes of
tail alterations lead to a constitutive high-affinity state. One
involves deletions or mutations of specific membrane-proximal residues
in the IIb or 3 tails, causing the
receptor to remain in a high-affinity state even if cellular ATP is
depleted. The other class involves replacement of the
IIb tail with certain other tails (eg,
5 or 6), but in this case the receptor
reverts to a low-affinity state upon depletion of ATP. This class of
energy-dependent, high-affinity mutants can also be inhibited by
overexpression of isolated 3 cytoplasmic tail chimeras,
suggesting that integrin affinity is being regulated by titratable
intracellular factors.114 This idea is supported by the
observation that IIb3-dependent adhesion of a megakaryocytic cell line is inhibited by cellular incorporation of
peptides derived from the membrane-distal region of the
3 tail.115
View larger version (7K):
[in this window]
[in a new window]
| Fig 4.
Amino acid sequences of the cytoplasmic tails of
IIb and 3. The space inserted into each
sequence arbitrarily separates the N-terminal membrane-proximal and
C-terminal membrane-distal regions, the significance of which is
discussed further in the text. Numbered residues are as in the
full-length integrin subunit.
|
|
These results suggest a working model in which the membrane-proximal
portions of the IIb and 3 tails normally
interact, possibly in part through a salt bridge, to form a hinge
through which signals impacting on membrane distal tail residues are
propagated across the membrane to modulate receptor affinity. Certain
membrane-proximal mutations or deletions break this hinge, leaving the
receptor in a permanent high-affinity state. Membrane-distal tail
residues might regulate receptor affinity in several ways: In
unstimulated cells, the IIb tail might bind a negative
regulator or interact with the 3 tail in such a way as
to prevent the action of a positive regulator. In stimulated cells, a
change in these relationships would either relieve the negative
constraint or trigger the function of the positive regulator. This
model predicts close but dynamic interactions between the
IIb and 3 tails. In fact, synthetic peptides derived from these tails do interact in
vitro.116,117
A number of proteins have been shown to bind directly to integrin
cytoplasmic tails, at least in vitro (Table
1), but there is no evidence yet that the endogenous forms of any of
these proteins modulate integrin affinity in cells. One such protein,
3-endonexin, binds selectively to the 3
tail and is present in platelets.118,119 Overexpression of
a 3-endonexin fusion protein in CHO cells increases the
affinity state of IIb3 and causes
fibrinogen-dependent cell aggregation.120 Although some of
the other proteins listed in Table 1 are present in platelets, it is
not known if they influence IIb3
affinity. Two proteins listed in the table may not be relevant to
IIb3, but they provide potential novel
links between integrins and cellular signaling pathways. Cytohesin-1
binds selectively to the 2 integrin tail and when
overexpressed in T lymphocytes, it increases cell adhesion through
L2.121 Cytohesin-1 contains a
PH domain, which binds 3-phosphorylated phosphoinositides, and a sec 7 domain, which binds the 2 tail and possesses guanine nucleotide exchange activity for a small GTP-ase,
ARF.122,123 One serine-threonine kinase, p59ILK
has been shown to bind to integrin tails, to inhibit
1-mediated cell adhesion, and to promote
anchorage-independent cell cycle progression and growth of epithelial
cells.124 These studies suggest that, in some cases,
integrins may be direct targets of protein kinases, phosphatases, or
GTPases. In this regard, the 3 cytoplasmic tail does
become phosphorylated on serine, threonine, and tyrosine residues in
thrombin-stimulated platelets.125-127 However, the
stoichiometry and functional significance of these events are not
clear. Furthermore, the tyrosine phosphorylation of 3 is
dependent on platelet aggregation; therefore, it is more likely to play
some role in outside-in signaling.
Several transmembrane or GPI-linked membrane proteins have been shown
to either coimmunoprecipitate with integrins or colocalize with them by
fluorescence microscopy (Table 2). These
associations may be direct or indirect, and several are relevant to
IIb3. CD47, also known as
integrin-associated protein, spans the platelet plasma membrane five
times and coimmunoprecipitates with 3
integrins.128 So far, no direct role for CD47 in
IIb3 function has been demonstrated, either in platelets or in the CHO cell model system.129
However, CD47 may function as a costimulatory agonist receptor in
platelets because binding of thrombospondin to CD47 leads to activation of IIb3 in a Gi-dependent
manner.130,131 CD98, a type II transmembrane protein
implicated in neutral amino acid transport and viral syncytia formation, was recently identified in a genetic screen by its ability
to complement dominant suppression of
IIb3 activation in CHO cells, but its
abundance in platelets is not known.132 CD9, a member of
the tetraspanin family of transmembrane proteins, colocalizes with
IIb3 in platelet -granule membranes
and filopodia.133 Antibodies to CD9 can stimulate platelet
aggregation in an Fc receptor-independent manner.134
However, tetraspanins may exist in multimolecular complexes, and the
interaction of CD9 with IIb3 may not be
direct. There is similar uncertainty in interpreting the reported
associations of integrins with caveolin or other proteins, such as Src
family kinases, that may become part of large complexes within
lipid-rich membrane microdomains.135,136 Thus, the
functional and physical relationships between
IIb3 and other proteins remain a fertile
area for further investigation.
| |
OUTSIDE-IN SIGNALING IN PLATELETS |
Platelet functions regulated by outside-in signaling.
Signaling through IIb3 determines the
extent to which platelets spread on a vascular matrix containing vWF or
fibrinogen and their resistance to detachment from the
matrix.5,137 Similarly, outside-in signals triggered during
platelet aggregation or spreading promote granule secretion and
secondary aggregation. Consequently, outside-in signals are a
determinant of the ultimate size of a hemostatic plug or a pathological
thrombus (Fig 1). The retraction of a fibrin clot also involves
outside-in signals because it represents the interaction of both fibrin
and the actin cytoskeleton with IIb3 and
the contraction of actin-myosin.138-140 Under certain conditions, even the development of platelet procoagulant activity due
to scrambling of membrane phospholipids is dependent, in part, on
events subsequent to platelet aggregation.141
The temporal and spatial hierarchy of outside-in signaling.
Outside-in signaling is initiated at localized regions of cell matrix
and cell-cell contact. In the platelet, it is triggered by
ligand-induced oligomerization of IIb3,
because only multivalent ligands are capable of inducing the
signal.38,142 Signaling is propagated by interactions
between integrin cytoplasmic tails, signaling molecules, and structural
cytoskeletal proteins, including vinculin, talin, and -actinin. The
initial signaling reactions foster continued assembly of the complex by
promoting protein-protein interactions, actin polymerization, and
cytoskeletal reorganization. Complex assembly continues until the
supply of new components is exhausted or a set of inhibitory signaling
reactions takes over, at which time the complex may even disassemble.
The platelet has provided a good model system to study outside-in
signaling and cytoskeletal reorganization in the absence of nuclear
signaling (Fig 5).143-145
Within seconds of binding soluble or immobilized fibrinogen or vWF,
platelets extend filopodia coincident with activation of Syk and
tyrosine phosphorylation of substrates of 50 to 68 kD and 140 kD.87,143,145,146 Shortly thereafter, the platelets begin
to flatten out or form microscopic aggregates. At this intermediate
stage, there is detectable activation of pp60Src, and
clusters of IIb3 are discernible by
immunofluorescence microscopy on the basal surfaces of the adherent
cells. Recent studies in CHO cell transfectants indicate that
fibrinogen binding can trigger activation of Syk in a manner that is
independent of ITAMs and actin polymerization, due to a combination of
autophosphorylation and phosphorylation by Src.147
View larger version (76K):
[in this window]
[in a new window]
| Fig 5.
Outside-in signaling through
IIb3 in platelets, emphasizing the
sequential nature of the process. First, agonists induce affinity
modulation and ligand binding promotes integrin clustering (1). Second,
the ligated and clustered integrins trigger early outside-in signaling
events, such as activation of Syk and Src (2). Although not shown, this
may be associated with filopodial extension. Finally, activation
and/or cytoskeletal translocation of FAK, protein tyrosine phosphatases
(PTP), and many other important enzymes (Etc.) occurs, coincident with
their assembly into mature focal adhesions that are connected to actin
stress fibers (3).
|
|
Platelet spreading on fibrinogen or vWF reaches a maximum after several
minutes, during which time the platelets display microscopic vinculin
clusters connected to F-actin cables, the platelet equivalent of focal
adhesions.91,146,148 Full spreading or aggregation is
associated with activation of the tyrosine kinase,
pp125FAK, and tyrosine phosphorylation of additional
substrates, including proteins of 101 and 105 kD, Tec (a tyrosine
kinase that contains a PH domain), and SHIP, an SH2 domain-containing
inositol 5-phosphatase.9,145,149,200 None of these changes
occur if spreading or aggregation is blocked. Eventually there is a
decrease in tyrosine phosphorylation of many substrates, due to
cytoskeletal recruitment and activation of protein tyrosine
phosphatases (eg, PTP-1B and SHP-1), and cleavage of protein tyrosine
kinases by calpain.54,146,150-152
FAK provides a well-studied example of how integrin-associated
signaling complexes may assemble.9,12,153 It contains a central catalytic domain flanked by N- and C-terminal domains. Subcellular localization of FAK is dictated by a focal adhesion targeting region in the C-terminal domain and possibly by a binding site for integrin tails in the N-terminal domain. FAK undergoes autophosphorylation at Y397 in response to cell adhesion,
providing a docking site for the SH2 domain of Src and possibly
PI-3-kinase. Src phosphorylates FAK at additional tyrosine residues,
creating sites for interaction of the adapter, Grb2. FAK also complexes
through proline-rich motifs in the C-terminal domain with the SH3
domains of the adaptors, p130cas and paxillin, and a Rho
GTPase-activating protein, GRAF. Indeed, p130cas and paxillin are
phosphorylated by the FAK/Src complex, enabling the recruitment of even
more proteins. FAK-null mice die in fetal life and, ex vivo, their
fibroblasts form focal adhesions but migrate poorly.154 In
platelets, activation of FAK requires both
IIb3 ligation and agonist receptor
occupancy, the latter being required to provide costimulatory signals
through Ca2+ and PKC.155
Studies of naturally occurring and experimentally induced mutations and
deletions in IIb3 provide strong evidence
for involvement of the IIb and 3
cytoplasmic tails in outside-in signaling.107,108,156 However, many fundamental questions remain. What is the role of tyrosine phosphorylation of the 3 tail in response to
platelet aggregation?127 Can certain protein or lipid
kinases and phosphatases couple directly to
IIb3? What are the effectors of Syk, Src,
and FAK? Whereas tyrosine phosphorylation is an early event in
outside-in signaling, there is an impressive and growing list of other
protein and lipid kinases, phosphatases, phospholipases, and GTP-ases that redistribute to the IIb3-rich core
cytoskeleton or become activated during platelet aggregation and
spreading.89,144,157-161,201 How are the functions of so
many proteins and their effectors integrated into the highly
coordinated response to platelet adhesion?
| |
PERSPECTIVE |
What are the practical implications of integrin signaling? Integrin
cytoplasmic tail mutations in patients with variant thrombasthenia prove that integrin signaling is required for hemostasis, but these
patients are very rare. However, other individuals with unexplained
platelet aggregation defects are encountered more frequently. Some of
these suffer from inherited defects, others from acquired disorders
that affect platelet function. Once an aggregation defect has been
established in the clinical laboratory, further evaluation can be
facilitated by conducting flow cytometry analyses of platelets, even in
whole blood. Fluorophore-conjugated reagents are available to
quantitate platelet surface antigens, including activation-specific
antigens (eg, P-selectin) and epitopes (eg, activated or
ligand-occupied IIb3).162
This allows facile categorization of the abnormality as either an
IIb3 activation defect or a postligand
binding defect.163 In the case of an activation defect, the
subsequent work-up can focus on specific agonist receptors and
biochemical pathways responsible for inside-out
signaling.164-166 In the case of a postligand
binding defect, the work-up can focus on the possibility of storage
pool disease or an abnormality in pathways triggered by integrin
ligation.107,167,168 We speculate that the spectrum of
clinical abnormalities in integrin signaling might even include
inappropriate increases in IIb3 function. For example, several dominant mutations introduced experimentally into
the IIb or 3 cytoplasmic tails result in
constitutive activation of the receptor, as discussed above. If such
mutations were to occur naturally, they might be responsible for some
cases of unexplained, chronic thrombocytopenia or even represent a risk
factor for arterial thrombosis.
Interest in IIb3 has expanded beyond the
realm of the hematologist because of the development of pharmacological
inhibitors of ligand binding to IIb3 for
prophylaxis and therapy of arterial thrombosis.169,170
Abciximab, a chimeric mouse-human antibody that blocks ligand binding
to IIb3, is already licensed for use as
adjunctive therapy in patients undergoing coronary angioplasty, and
additional parenteral and orally active compounds are now in clinical
trials. It is too early to predict the full range of indications for
these agents or the degree of efficacy and risk of long-term use, but
it is satisfying that platelet research has yielded the first
integrin-based therapeutics. In this context, the orally active
antiplatelet agents currently available in developed countries are, in
one way or another, inhibitors of inside-out integrin signaling:
aspirin inhibits cyclooxygenase-1 and, ultimately, the production of
thromboxane A2; ticlopidine and clopidogrel inhibit
signaling through the ADP receptor171; and
phosphodiesterase inhibitors decrease catabolism of cyclic AMP, a
suppressor of platelet activation. If the intracellular events
responsible for IIb3 signaling can be
better defined, it may be possible to identify new integrin-proximal
signaling proteins as drug targets.
| |
FOOTNOTES |
Submitted October 9, 1997;
accepted December 19, 1997.
Address reprint requests to Sanford J. Shattil, MD, Department of
Vascular Biology, The Scripps Research Institute, 10550 N Torrey Pines
Rd, VB-5, La Jolla, CA 92037.
| |
ACKNOWLEDGMENT |
The authors are grateful to our collaborators, past and present, and in
particular Joan Brugge and Mark Ginsberg, for many of the concepts
summarized herein, and to Mark Ginsberg and Martin Schwartz for
critical review of the manuscript. Cited work from the authors'
laboratory was supported by National Institutes of Health Grants No.
HL56595 and HL57900 and from Cor Therapeutics, Inc.
| |
REFERENCES |
1.
Martin P:
Wound healing Aiming for perfect skin regeneration.
Science
276:75,
1997[Abstract/Free Full Text]
2.
Diacovo TG,
Roth SJ,
Buccola JM,
Bainton DF,
Springer TA:
Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta2-integrin CD11b/CD18.
Blood
88:146,
1996[Abstract/Free Full Text]
3.
McEver RP,
Cummings RD:
Perspectives series: Cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment.
J Clin Invest
100:485,
1997[Medline]
[Order article via Infotrieve]
4.
Frenette PS,
Johnson RC,
Hynes RO,
Wagner DD:
Platelets roll on stimulated endothelium in vivo: An interaction mediated by endothelial P-selectin.
Proc Natl Acad Sci USA
92:7450,
1995[Abstract/Free Full Text]
5.
Savage B,
Saldívar E,
Ruggeri ZM:
Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor.
Cell
84:289,
1996[Medline]
[Order article via Infotrieve]
6. Ruggeri ZM, FitzGerald GA, Shattil SJ: Platelet thrombus
formation and anti-platelet therapy, in Chien KR, Breslow JL, Leiden
JM, Rosenberg RD, Seidman C, Braunwald E (eds): Molecular Basis of
Heart Disease. Philadelphia, PA, Saunders (in press)
7.
Hynes RO:
Integrins: Versatility, modulation, and signaling in cell adhesion.
Cell
69:11,
1992[Medline]
[Order article via Infotrieve]
8.
Schwartz MA,
Schaller MD,
Ginsberg MH:
Integrins: Emerging paradigms of signal transduction.
Annu Rev Cell Biol
11:549,
1995[Medline]
[Order article via Infotrieve]
9.
Clark EA,
Brugge JS:
Integrins and signal transduction pathways. The road taken.
Science
268:233,
1995[Abstract/Free Full Text]
10.
Sastry SK,
Horwitz AF:
Adhesion-growth factor interactions during differentiation: An integrated biological response.
Dev Biol
180:455,
1996[Medline]
[Order article via Infotrieve]
11.
Yamada KM,
Geiger B:
Molecular interactions in cell adhesion complexes.
Curr Opin Cell Biol
9:76,
1997[Medline]
[Order article via Infotrieve]
12. Schlaepfer DD, Hunter T: Integrin signaling and tyrosine
phosphorylation: Just the FAKs? Trends Cell Biol (in
press)
13. Brass LF: Molecular basis for platelet activation, in Hoffman R,
Benz E, Shattil S, Furie B, Cohen H, Silberstein L (eds): Hematology.
Basic Principles and Practice. New York, NY, Churchill-Livingstone,
1995, p 1536
14. (suppl 4)
Fox JEB:
Platelet activation: New aspects.
Haemostasis
26:102,
1996
15.
Parise LV,
Phillips DR:
Reconstitution of the purified platelet fibrinogen receptor. Fibrinogen binding properties of the glycoprotein IIb-IIIa complex.
J Biol Chem
260:10698,
1985[Abstract/Free Full Text]
16.
Weisel JW,
Nagaswami C,
Vilaire G,
Bennett JS:
Examination of the platelet membrane glycoprotein IIb-IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy.
J Biol Chem
267:16637,
1992[Abstract/Free Full Text]
17.
Plow EF,
D'Souza SE,
Ginsberg MH:
Ligand binding to GP IIb-IIIa: A status report.
Semin Thromb Hemost
18:324,
1992[Medline]
[Order article via Infotrieve]
18.
Bennett JS,
Vilaire G:
Exposure of platelet fibrinogen receptors by ADP and epinephrine.
J Clin Invest
64:1393,
1979
19.
Neri D,
Montigiani S,
Kirkham PM:
Biophysical methods for the determination of antigen-antibody affinites.
Trends Biochem Sci
14:465,
1996
20.
Miyamoto S,
Teramoto H,
Gutkind JS,
Yamada KM:
Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: Roles of integrin aggregation and occupancy of receptors.
J Cell Biol
135:1633,
1996[Abstract/Free Full Text]
21.
Juliano R:
Cooperation between soluble factors and integrin-mediated cell anchorage in the control of cell growth and differentiation.
Bioassays
18:911,
1996[Medline]
[Order article via Infotrieve]
22.
Peerschke EI:
Regulation of platelet aggregation by post-fibrinogen binding events.
Thromb Haemost
73:862,
1995[Medline]
[Order article via Infotrieve]
23.
Wagner CL,
Mascelli MA,
Neblock DS,
Weisman HF,
Coller BS,
Jordan RE:
Analysis of GP IIb/IIIa receptor number by quantification of 7E3 binding to human platelets.
Blood
88:907,
1996[Abstract/Free Full Text]
24.
Frojmovic M,
Wong T,
Van de Ven T:
Dynamic measurements of the platelet membrane glycoprotein IIb-IIIa receptor for fibrinogen by flow cytometry. I. Methodology, theory and results for two distinct activators.
Biophys J
59:815,
1991[Medline]
[Order article via Infotrieve]
25.
Nurden AT:
Association of fibrinogen-bound glycoprotein IIb-IIIa complexes on the activated platelet surface.
J Lab Clin Med
128:7,
1996[Medline]
[Order article via Infotrieve]
26.
Kleiman NS,
Raizner AE,
Jordan R,
Wang AL,
Norton D,
Mace KF,
Joshi A,
Coller BS,
Weisman HF:
Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: Implications for inhibition of the internal pool of GPIIb/IIIa receptors.
J Am Coll Cardiol
26:1665,
1995[Abstract]
27.
Woods VL,
Wolff LE,
Keller DM:
Resting platelets contain a substantial centrally located pool of glycoprotein IIb-IIIa complex which may be accessible to some but not other extracellular proteins.
J Biol Chem
261:15242,
1986[Abstract/Free Full Text]
28.
Diamond MS,
Springer TA:
The dynamic regulation of integrin adhesiveness.
Curr Biol
4:506,
1994[Medline]
[Order article via Infotrieve]
29.
van Kooyk Y,
Figdor CG:
Signalling and adhesive properties of the integrin leucocyte function-associated antigen 1 (LFA-1).
Biochem Soc Trans
25:515,
1997[Medline]
[Order article via Infotrieve]
30.
Peerschke EIB:
Stabilization of platelet-fibrinogen interactions is an integral property of the glycoprotein IIb-IIIa complex.
J Lab Clin Med
124:439,
1994[Medline]
[Order article via Infotrieve]
31.
Müller B,
Zerwes H-G,
Tangemann K,
Peter J,
Engel J:
Two-step binding mechanism of fibrinogen to IIb3 integrin reconstituted into planar lipid bilayers.
J Biol Chem
268:6800,
1993[Abstract/Free Full Text]
32.
Simmons SR,
Albrecht RM:
Self-association of bound fibrinogen on platelet surfaces.
J Lab Clin Med
128:39,
1996[Medline]
[Order article via Infotrieve]
33.
Peerschke EIB:
Bound fibrinogen distribution on stimulated plateletsExamination by confocal scanning laser microscopy.
Am J Pathol
147:678,
1995[Abstract]
34.
Fox J,
Shattil SJ,
Kinlough-Rathbone R,
Richardson M,
Packham MA,
Sanan DA:
The platelet cytoskeleton stabilizes the interaction between IIb3 and its ligand and induces selective movements of ligand-occupied integrin.
J Biol Chem
271:7004,
1996[Abstract/Free Full Text]
35.
Kucik DF,
Dustin ML,
Miller JM,
Brown EJ:
Adhesion-activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes.
J Clin Invest
97:2139,
1996[Medline]
[Order article via Infotrieve]
36.
Wencel-Drake JD,
Boudignon-Proudhon C,
Dieter MG,
Criss AB,
Parise LV:
Internalization of bound fibrinogen modulates platelet aggregation.
Blood
87:602,
1996[Abstract/Free Full Text]
37.
Leung L,
Nachman R:
Molecular mechanisms of platelet aggregation.
Annu Rev Med
37:179,
1986[Medline]
[Order article via Infotrieve]
38.
Abrams C,
Deng J,
Steiner B,
Shattil SJ:
Determinants of specificity of a baculovirus-expressed antibody Fab fragment that binds selectively to the activated form of integrin IIb3.
J Biol Chem
269:18781,
1994[Abstract/Free Full Text]
39.
Sims PJ,
Ginsberg MH,
Plow EF,
Shattil SJ:
Effect of platelet activation on the conformation of the plasma membrane glycoprotein IIb-IIIa complex.
J Biol Chem
266:7345,
1991[Abstract/Free Full Text]
40.
Du X,
Gu M,
Weisel J,
Nagaswami C,
Bennett JS,
Bowditch R,
Ginsberg MH:
Long range propagation of conformational changes in integrin IIb3.
J Biol Chem
268:23087,
1993[Abstract/Free Full Text]
41.
Springer TA:
Folding of the N-terminal, ligand-binding region of integrin -subunits into a -propeller domain.
Proc Natl Acad Sci USA
94:65,
1997[Abstract/Free Full Text]
42.
Tozer EC,
Liddington RC,
Sutcliffe MJ,
Smeeton AH,
Loftus JC:
Ligand binding to integrin IIb3 is dependent on a MIDAS-like domain in the 3 subunit.
J Biol Chem
271:21978,
1996[Abstract/Free Full Text]
43.
Lee JO,
Riev P,
Aranout MA,
Liddington R:
Crystal structure of the A-domain from the A-subunit of integrin CR3 (CD11B/CD18).
Cell
80:631,
1995[Medline]
[Order article via Infotrieve]
44.
Qu AD,
Leahy DJ:
The role of divalent cation in the structure of the I-domain from the CD11a/CD18 integrin.
Structure
4:931,
1996[Medline]
[Order article via Infotrieve]
45.
Loftus JC,
Liddington RC:
Cell adhesion in vascular biology. New insights into integrin-ligand interaction.
J Clin Invest
99:2302,
1997[Medline]
[Order article via Infotrieve]
46.
Farrell DH,
Thiagarajan P,
Chung DW,
Davie EW:
Role of fibrinogen and chain sites in platelet aggregation.
Proc Natl Acad Sci USA
89:10729,
1992[Abstract/Free Full Text]
47.
Rooney MM,
Parise LV,
Lord ST:
Dissecting clot retraction and platelet aggregationClot retraction does not require an intact fibrinogen gamma chain.
J Biol Chem
271:8553,
1996[Abstract/Free Full Text]
48.
Ugarova TP,
Budzynski AZ,
Shattil SJ,
Ruggeri ZM,
Ginsberg MH,
Plow EF:
Conformational changes in fibrinogen elicited by its interaction with platelet membrane glycoprotein GPIIb-IIIa.
J Biol Chem
268:21080,
1993[Abstract/Free Full Text]
49.
Savage B,
Bottini E,
Ruggeri ZM:
Interaction of integrin IIb3 with multiple fibrinogen domains during platelet adhesion.
J Biol Chem
270:28812,
1995[Abstract/Free Full Text]
50.
Hung DT,
Vu T-KH,
Wheaton VI,
Ishii K,
Coughlin SR:
Cloned platelet thrombin receptor is necessary for thrombin-induced platelet activation.
J Clin Invest
89:1350,
1992
51.
Brass LF,
Manning DR,
Cichowski K,
Abrams CS:
Signaling through G proteins in platelets: To the integrins and beyond.
Thromb Haemost
78:581,
1997[Medline]
[Order article via Infotrieve]
52.
Gachet C,
Hechler B,
Léon C,
Vial C,
Leray C,
Ohlmann P,
Cazenave JP:
Activation of ADP receptors and platelet function.
Thromb Haemost
78:271,
1997[Medline]
[Order article via Infotrieve]
53.
Offermanns S,
Toombs CF,
Hu YH,
Simon MI:
Defective platelet activation in Gq-deficient mice.
Nature
389:183,
1997[Medline]
[Order article via Infotrieve]
54.
Jackson SP,
Schoenwaelder SM,
Yuan YP,
Salem HH,
Cooray P:
Non-receptor protein tyrosine kinases and phosphatases in human platelets.
Thromb Haemost
76:640,
1996[Medline]
[Order article via Infotrieve]
55.
Raja S,
Avraham S,
Avraham H:
Tyrosine phosphorylation of the novel protein-tyrosine kinase RAFTK during an early phase of platelet activation by an integrin glycoprotein IIb-IIIa-independent mechanism.
J Biol Chem
272:10941,
1997[Abstract/Free Full Text]
56.
Tate BF,
Rittenhouse SE:
Thrombin activation of human platelets causes tyrosine phosphorylation of PLC-gamma2.
Biochim Biophys Acta Mol Cell Res
1178:281,
1993[Medline]
[Order article via Infotrieve]
57.
Cichowski K,
Brugge JS,
Brass LF:
Thrombin receptor activation and integrin engagement stimulate tyrosine phosphorylation of the proto-oncogene product, p95vav, in platelets.
J Biol Chem
271:7544,
1996[Abstract/Free Full Text]
58.
Rosa JP,
Artcanuthurry V,
Grelac F,
Maclouf J,
Caen JP,
Lévy-Toledano S:
Reassessment of protein tyrosine phosphorylation in thrombasthenic platelets: Evidence that phosphorylation of cortactin and a 64-kD protein is dependent on thrombin activation and integrin IIb3.
Blood
89:4385,
1997[Abstract/Free Full Text]
59.
Lerea KM,
Tonks NK,
Krebs EG,
Fischer EH,
Glomset JA:
Vanadate and molybdate increase tyrosine phosphorylation in a 50-kilodalton protein and stimulate secretion in electropermeabilized platelets.
Biochemistry
28:9286,
1989[Medline]
[Order article via Infotrieve]
60. (abstr, suppl 1)
Law DA,
Nannizzi-Alaimo L,
Ministri K,
Hughes P,
Turner M,
Shattil SJ,
Ginsberg MH,
Tybulewicz V,
Phillips DR:
Syk-deficient platelets demonstrate a role for Syk in IIb3 inside-out signaling and highlight the lack of specificity of the tyrosine kinase inhibitor, piceatannol.
Blood
90:425a,
1997
61.
Huang M-M,
Indik Z,
Brass LF,
Hoxie JA,
Schrieber AD,
Brugge JS:
Activation of FcRII induces tyrosine phosphorylation of multiple proteins including FcRII.
J Biol Chem
267:5467,
1992[Abstract/Free Full Text]
62.
Chacko GW,
Brandt JT,
Coggeshall KM,
Anderson CL:
Phosphoinositide 3-kinase and p72syk noncovalently associate with the low affinity Fcgamma receptor on human platelets through an immunoreceptor tyrosine-based activation motifReconstitution with synthetic phosphopeptides.
J Biol Chem
271:10775,
1996[Abstract/Free Full Text]
63.
Ruggeri ZM:
Mechanisms initiating platelet thrombus formation.
Thromb Haemost
78:611,
1997[Medline]
[Order article via Infotrieve]
64.
Rand JH,
Glanville RW,
Wu XX,
Ross JM,
Zangari M,
Gordon RE,
Schwartz E,
Potter BJ:
The significance of subendothelial von Willebrand factor.
Thromb Haemost
78:445,
1997[Medline]
[Order article via Infotrieve]
65.
Santoro SA,
Zutter MM:
The 21 integrin: A collagen receptor on platelets and other cells.
Thromb Haemost
74:813,
1995[Medline]
[Order article via Infotrieve]
66.
Diaz-Ricart M,
Tandon NN,
Carretero M,
Ordinas A,
Bastida E,
Jamieson GA:
Platelets lacking functional CD36 (glycoprotein IV) show reduced adhesion to collagen in flowing whole blood.
Blood
82:491,
1993[Abstract/Free Full Text]
67.
Moroi M,
Jung SM:
Platelet receptors for collagen.
Thromb Haemost
78:439,
1997[Medline]
[Order article via Infotrieve]
68.
Tsuji M,
Ezumi Y,
Arai M,
Takayama H:
A novel association of Fc receptor gamma-chain with glycoprotein VI and their co-expression as a collagen receptor in human platelets.
J Biol Chem
272:23528,
1997[Abstract/Free Full Text]
69.
Gibbins JM,
Okuma M,
Farndale R,
Barnes M,
Watson SP:
Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor gamma-chain.
FEBS Lett
413:255,
1997[Medline]
[Order article via Infotrieve]
70.
Gibbins J,
Asselin J,
Farndale R,
Barnes M,
Law CL,
Watson SP:
Tyrosine phosphorylation of the Fc receptor gamma-chain in collagen-stimulated platelets.
J Biol Chem
271:18095,
1996[Abstract/Free Full Text]
71.
Asselin J,
Gibbins JM,
Achison M,
Lee YH,
Morton LF,
Farndale RW,
Barnes MJ,
Watson SP:
Collagen-like peptide stimulates tyrosine phosphorylation of syk and phospholipase Cgamma2 in platelets independent of the integrin 21.
Blood
89:1235,
1997[Abstract/Free Full Text]
72.
Polgar J,
Clemetson JM,
Kehrel BE,
Wiedemann M,
Magnenat EM,
Wells TNC,
Clemetson KJ:
Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor.
J Biol Chem
272:13576,
1997[Abstract/Free Full Text]
73.
Poole A,
Gibbins JM,
Turner M,
van Vugt MJ,
van den Winkel JGJ,
Saito T,
Tybulewicz VLJ,
Watson SP:
The Fc receptor -chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen.
EMBO J
16:2333,
1997[Medline]
[Order article via Infotrieve]
74.
Ozaki Y,
Satoh K,
Yatomi Y,
Miura S,
Fujimura Y,
Kume S:
Protein tyrosine phosphorylation in human platelets induced by interaction between glycoprotein Ib and von Willebrand factor.
Biochim Biophys Acta
1243:482,
1995[Medline]
[Order article via Infotrieve]
75.
Shattil SJ,
Brass LF:
Induction of the fibrinogen receptor on human platelets by intracellular mediators.
J Biol Chem
262:992,
1987[Abstract/Free Full Text]
76.
Shiraga M,
Tomiyama Y,
Honda S,
Kashiwagi H,
Kosugi S,
Handa M,
Ikeda Y,
Kanakura Y,
Kurata Y,
Matsuzawa Y:
Affinity modulation of the platelet integrin alpha IIb beta 3 by alpha-chymotrypsin: A possible role for Na+/Ca2+ exchanger.
Blood
88:2594,
1996[Abstract/Free Full Text]
77.
Shattil SJ,
Cunningham M,
Wiedmer T,
Zhao J,
Sims PJ,
Brass LF:
Regulation of glycoprotein IIb-IIIa receptor function studied with platelets permeabilized by the pore-forming complement proteins C5b-9.
J Biol Chem
267:18424,
1992[Abstract/Free Full Text]
78.
Hemmings BA:
Update: Signal transductionPH domainsA universal membrane adapter.
Science
275:1899,
1997[Free Full Text]
79.
Li JX,
Zhu ZX,
Bao ZH:
Role of MacMARCKS in integrin-dependent macrophage spreading and tyrosine phosphorylation of paxillin.
J Biol Chem
271:12985,
1996[Abstract/Free Full Text]
80.
Rittenhouse SE:
Phosphoinositide 3-kinase activation and platelet function.
Blood
88:4401,
1996[Free Full Text]
81.
Shimizu Y,
Hunt SW III:
Regulating integrin-mediated adhesion: One more function for PI 3-kinase?
Immunol Today
17:565,
1996[Medline]
[Order article via Infotrieve]
82.
Tang XW,
Downes CP:
Purification and characterization of Ggamma-responsive phosphoinositide 3-kinases from pig platelet cytosol.
J Biol Chem
272:14193,
1997[Abstract/Free Full Text]
83.
Gutkind JS,
Lacal PM,
Robbins KC:
Thrombin-dependent association of phosphatidylinositol-3 kinase with p60c-src and p59fyn in human platelets.
Mol Cell Biol
10:3806,
1990[Abstract/Free Full Text]
84.
Yanagi S,
Sada K,
Tohyama Y,
Tsubokawa M,
Nagai K,
Yonezawa K,
Yamamura H:
Translocation, activation and association of protein-tyrosine kinase (p72syk) with phosphatidylinositol 3-kinase are early events during platelet activation.
Eur J Biochem
224:329,
1994[Medline]
[Order article via Infotrieve]
85.
Toker A,
Cantley LC:
Signaling through the lipid products of phosphoinositides.
Nature
387:673,
1997[Medline]
[Order article via Infotrieve]
86. (abstr, suppl 1)
Kovacsovics TJ,
Hartwig JH,
Cantley LC,
Toker A:
Irreversible platelet aggregation and prolonged pleckstrin phosphorylation are mediated by the lipid products of phosphphatidylinositol 3-kinase.
Blood
86:454a,
1995
87.
Hartwig JH,
Kung S,
Kovacsovics T,
Janmey PA,
Cantley LC,
Stossel TP,
Toker A:
D3 phosphoinositides and outside-in integrin signaling by glycoprotein IIb-IIIa mediate platelet actin assembly and filopodial extension induced by phorbol 12-myristate 13-acetate.
J Biol Chem
271:32986,
1996[Abstract/Free Full Text]
88.
Toker A,
Bachelot C,
Chen CS,
Falck JR,
Hartwig JH,
Cantley LC,
Kovacsovics TJ:
Phosphorylation of the platelet p47 phosphoprotein is mediated by the lipid products of phosphoinositide 3-kinase.
J Biol Chem
270:29525,
1995[Abstract/Free Full Text]
89.
Hartwig JH,
Bokoch GM,
Carpenter CL,
Janmey PA,
Taylor LA,
Toker A,
Stossel TP:
Thrombin receptor ligation and activated rac uncap actin filament barbed ends through phosphoinositide synthesis in permeabilized human platelets.
Cell
82:643,
1995[Medline]
[Order article via Infotrieve]
90. Morii N, Teru-uchi T, Tominaga T, Kumagai N, Kozaki S, Ushikubi
F, Narumiya S: A rho gene product in human blood platelets. II.
Effects of the ADP-ribosylation by botulinum C3 ADP-ribosyltransferase
on platelet aggregation. J Biol Chem 267:20921, 1992
91. Leng L, Kashiwagi H, Ren X-D, Shattil SJ: Rho A and the function
of platelet integrin IIb3. Blood (in press)
92.
Machesky LM,
Hall A:
Rho: A connection between membrane receptor signalling and the cytoskeleton.
Trends Cell Biol
6:304,
1996 [Medline]
[Order article via Infotrieve]
93.
Zhang Z,
Vuori K,
Wang H-G,
Reed JC,
Ruoshlati E:
Integrin activation by R-ras.
Cell
85:61,
1996[Medline]
[Order article via Infotrieve]
94.
Shock DD,
He K,
Wencel-Drake JD,
Parise LV:
Ras activation in platelets following stimulation of the thrombin receptor, thromboxane A2 receptor or protein kinase C.
Biochem J
321:525,
1997
95.
Franke B,
Akkerman JWN,
Bos JL:
Rapid Ca2+-mediated activation of Rap1 in human platelets.
EMBO J
16:252,
1997[Medline]
[Order article via Infotrieve]
96.
Papkoff J,
Chen R-H,
Blenis J,
Forsman J:
p42 mitogen-activated protein kinase and p90 ribosomal S6 kinase are selectively phosphorylated and activated during thrombin-induced platelet activation and aggregation.
Mol Cell Biol
14:463,
1994[Abstract/Free Full Text]
97.
Hughes PE,
Renshaw MW,
Pfaff M,
Forsyth J,
Keivens VM,
Schwartz MA,
Ginsberg MH:
Suppression of integrin activation: A novel function of a Ras/Raf-initiated MAP-kinase pathway.
Cell
88:521,
1996
98.
Nadal F,
Levy-Toledano S,
Grelac F,
Caen JP,
Rosa JP,
Bryckaert M:
Negative regulation of mitogen-activated protein kinase activation by integrin IIb3 in platelets.
J Biol Chem
272:22381,
1997[Abstract/Free Full Text]
99.
Freedman JE,
Loscalzo J,
Barnard MR,
Alpert C,
Keaney JF Jr,
Michelson AD:
Nitric oxide released from activated platelets inhibits platelet recruitment.
J Clin Invest
100:350,
1997[Medline]
[Order article via Infotrieve]
100.
Freedman JE,
Loscalzo J,
Benoit SE,
Valeri R,
Barnard MR,
Michelson AD:
Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis.
J Clin Invest
97:979,
1996[Medline]
[Order article via Infotrieve]
101.
Haffner C,
Jarchau T,
Reinhard M,
Hoppe J,
Lohmann SM,
Walter U:
Molecular cloning, structural analysis and functional expression of the proline-rich focal adhesion and microfilament-associated protein VASP.
EMBO J
14:19,
1995[Medline]
[Order article via Infotrieve]
102.
Eigenthaler M,
Walter U:
Signal transduction and cyclic nucleotides in human platelets.
Thromb Haemorrh Disorders
8:41,
1994
103.
Van Willigen G,
Akkerman J-WN:
Protein kinase C and cyclic AMP regulate reversible exposure of binding sites for fibrinogen on the glycoprotein IIb-IIIa complex of human platelets.
Biochem J
273:115,
1991
104.
Marcus AJ,
Broekman MJ,
Drosopoulos JHF,
Islam N,
Alyonycheva TN,
Safier LB,
Hajjar KA,
Posnett DN,
Schoenborn MA,
Schooley KA,
Gayle RB,
Maliszewski CR:
The endothelial cell ecto-ADPase responsible for inhibition of platelet function is CD39.
J Clin Invest
99:1351,
1997[Medline]
[Order article via Infotrieve]
105.
Vassbotn FS,
Havnen OK,
Heldin C-H,
Holmsen H:
Negative feedback regulation of human platelets via autocrine activation of the platelet-derived growth factor -receptor.
J Biol Chem
269:13874,
1994[Abstract/Free Full Text]
106.
Chen Y-P,
Djaffar I,
Pidard D,
Steiner B,
Cieutat A-M,
Caen JP,
Rosa J-P:
Ser-752  Pro mutation in the cytoplasmic domain of integrin 3 subunit and defective activation of platelet integrin IIb 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia.
Proc Natl Acad Sci USA
89:10169,
1992[Abstract/Free Full Text]
107.
Wang R,
Shattil SJ,
Ambruso DR,
Newman PJ:
Truncation of the cytoplasmic domain of 3 in a variant form of Glanzmann thrombasthenia abrogates signaling through the integrin IIb3 complex.
J Clin Invest
100:2393,
1997[Medline]
[Order article via Infotrieve]
108.
Chen Y-P,
O'Toole TE,
Ylänne J,
Rosa J-P,
Ginsberg MH:
A point mutation in the integrin 3 cytoplasmic domain (S752P) impairs bidirectional signaling through IIb 3 (platelet glycoprotein IIb-IIIa).
Blood
84:1857,
1994[Abstract/Free Full Text]
109.
O'Toole TE,
Katagiri Y,
Faull RJ,
Peter K,
Tamura R,
Quaranta V,
Loftus JC,
Shattil SJ,
Ginsberg MH:
Integrin cytoplasmic domains mediate inside-out signaling.
J Cell Biol
124:1047,
1994[Abstract/Free Full Text]
110.
O'Toole TE,
Ylanne J,
Culley BM:
Regulation of integrin affinity states through an NPXY motif in the subunit cytoplasmic domain.
J Biol Chem
270:8553,
1995[Abstract/Free Full Text]
111.
Hughes PE,
O'Toole TE,
Ylanne J,
Shattil SJ,
Ginsberg MH:
The conserved membrane-proximal region of an integrin cytoplasmic domain specifies ligand-binding affinity.
J Biol Chem
270:12411,
1995[Abstract/Free Full Text]
112.
Hughes PE,
Diaz-Gonzalez F,
Leong L,
Wu CY,
McDonald JA,
Shattil SJ,
Ginsberg MH:
Breaking the integrin hingeA defined structural constraint regulates integrin signaling.
J Biol Chem
271:6571,
1996[Abstract/Free Full Text]
113.
Loh E,
Qi WW,
Vilaire G,
Bennett JS:
Effect of cytoplasmic domain mutations on the agonist-stimulated ligand binding activity of the platelet integrin IIb3.
J Biol Chem
271:30233,
1996[Abstract/Free Full Text]
114.
Chen Y-P,
O'Toole TE,
Shipley T,
Forsyth J,
LaFlamme SE,
Yamada KM,
Shattil SJ,
Ginsberg MH:
"Inside-out" signal transduction inhibited by isolated integrin cytoplasmic domains.
J Biol Chem
269:18307,
1994[Abstract/Free Full Text]
115.
Liu XY,
Timmons S,
Lin YZ,
Hawiger J:
Identification of a functionally important sequence in the cytoplasmic tail of integrin 3 by using cell-permeable peptide analogs.
Proc Natl Acad Sci USA
93:11819,
1996[Abstract/Free Full Text]
116.
Muir TW,
Williams MJ,
Ginsberg MH,
Kent SBH:
Design and chemical synthesis of a neoprotein structural model for the cytoplasmic domain of a multisubunit cell-surface receptor: Integrin IIb3 (platelet GPIIb-IIIa).
Biochemistry
33:7701,
1994[Medline]
[Order article via Infotrieve]
117.
Haas TA,
Plow EF:
The cytoplasmic domain of IIb3. A ternary complex of the integrin alpha and beta subunits and a divalent cation.
J Biol Chem
271:6017,
1996[Abstract/Free Full Text]
118.
Shattil SJ,
O'Toole T,
Eigenthaler M,
Thon V,
Williams M,
Babior BM,
Ginsberg MH:
3-endonexin, a novel polypeptide that interacts specifically with the cytoplasmic tail of the integrin 3 subunit.
J Cell Biol
131:807,
1995[Abstract/Free Full Text]
119.
Eigenthaler M,
Hofferer L,
Shattil SJ,
Ginsberg MH:
A conserved sequence motif in the integrin 3 cytoplasmic domain is required for its specific interaction with 3-endonexin.
J Biol Chem
272:7693,
1997[Abstract/Free Full Text]
120.
Kashiwagi H,
Schwartz MA,
Eigenthaler MA,
Davis KA,
Ginsberg MH,
Shattil SJ:
Affinity modulation of platelet integrin IIb3 by 3-endonexin, a selective binding partner of the 3 integrin cytoplasmic tail.
J Cell Biol
137:1433,
1997[Abstract/Free Full Text]
121.
Kolanus W,
Nagel W,
Schiller B,
Zeitlmann L,
Godar S,
Stockinger H,
Seed B:
Alpha-L-Beta-2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule.
Cell
86:233,
1996[Medline]
[Order article via Infotrieve]
122.
Klarlund JK,
Guilherme A,
Holik JJ,
Virbasius JV,
Chawla A,
Czech MP:
Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains.
Science
275:1927,
1997[Abstract/Free Full Text]
123.
Meacci E,
Tsai SC,
Adamik R,
Moss J,
Vaughn M:
Cytohesin-1, a cytosolic guanine nucleotide-exchange protein for ADP-ribosylation factor.
Proc Natl Acad Sci USA
94:1745,
1997[Abstract/Free Full Text]
124.
Radeva G,
Petrocelli T,
Behrend E,
Leung-Hagesteijn C,
Filmus J,
Slingerland J,
Dedhar S:
Overexpression of the integrin-linked kinase promotes anchorage-independent cell cycle progression.
J Biol Chem
272:13937,
1997[Abstract/Free Full Text]
125.
Hillery CA,
Smyth SS,
Parise LV:
Phosphorylation of human platelet glycoprotein IIIa (GPIIIa). Dissociation from fibrinogen receptor activation and phosphorylation of GPIIIa in vitro.
J Biol Chem
266:14663,
1991[Abstract/Free Full Text]
126.
Van Willigen G,
Hers I,
Gorter G,
Akkerman J-WN:
Exposure of ligand-binding sites on platelet integrin IIb/3 by phosphorylation of the 3 subunit.
Biochem J
314:769,
1996
127.
Law DA,
Nannizzi-Alaimo L,
Phillips DR:
Outside-in signal transduction: IIb3 (GP IIb-IIIa) tyrosine phosphorylation induced by platelet aggregation.
J Biol Chem
271:10811,
1996[Abstract/Free Full Text]
128.
Lindberg FP,
Lublin DM,
Telen MJ,
Veile RA,
Miller YE,
Donis-Keller H,
Brown EJ:
Rh-related antigen CD47 is the signal-transducer integrin-associated protein.
J Biol Chem
269:1567,
1994[Abstract/Free Full Text]
129.
Fujimoto T,
Fujimura K,
Noda M,
Takafuta T,
Shimomura T,
Kuramoto A:
50-kD integrin-associated protein does not detectably influence several functions of glycoprotein IIb-IIIa complex in human platelets.
Blood
86:2174,
1995[Abstract/Free Full Text]
130.
Chung J,
Gao AG,
Frazier WA:
Thrombospondin acts via integrin-associated protein to activate the platelet integrin IIb3.
J Biol Chem
272:14740,
1997[Abstract/Free Full Text]
131.
Dorahy DJ,
Thorne RF,
Fecondo JV,
Burns GF:
Stimulation of platelet activation and aggregation by a carboxy-terminal peptide from thrombospondin binding to the integrin-associated protein receptor.
J Biol Chem
272:1323,
1997[Abstract/Free Full Text]
132.
Fenczik CA,
Ramos JW,
Ginsberg MH:
Complementation of dominant suppression implicates CD98 in integrin activation.
Nature
390:81,
1997[Medline]
[Order article via Infotrieve]
133.
Brisson C,
Azorsa DO,
Jennings LK,
Moog S,
Cazenave JP,
Lanza F:
Co-localization of CD9 and GPIIb-IIIa (IIb 3 integrin) on activated platelet pseudopods and -granule membranes.
Histochem J
29:153,
1997[Medline]
[Order article via Infotrieve]
134.
Slupsky JR,
Kamiguti AS,
Rhodes NP,
Cawley JC,
Shaw ARE,
Zuzel M:
The platelet antigens CD9, CD42 and integrin IIb IIIa can be topographically associated and transduce functionally similar signals.
Eur J Biochem
244:168,
1997[Medline]
[Order article via Infotrieve]
135.
Wary KK,
Mainiero F,
Isakoff SJ,
Marcantonio EE,
Giancotti FG:
The adaptor protein Shc couples a class of integrins to the control of cell cycle progression.
Cell
87:733,
1996[Medline]
[Order article via Infotrieve]
136.
Dorahy DJ,
Berndt MC,
Burns GF:
Capture by chemical crosslinkers provides evidence that integrin IIb3 forms a complex with protein tyrosine kinases in intact platelets.
Biochem J
309:481,
1995
137.
Savage B,
Shattil SJ,
Ruggeri ZM:
Modulation of platelet function through adhesion receptors. A dual role for glycoprotein IIb-IIIa (integrin IIb3) mediated by fibrinogen and glycoprotein Ib-von Willebrand factor.
J Biol Chem
267:11300,
1992[Abstract/Free Full Text]
138.
Cohen I,
Gerrard JM,
White JG:
Ultrastructure of clots during isometric contraction.
J Cell Biol
93:775,
1982[Abstract/Free Full Text]
139.
Chen Y-P,
O'Toole TE,
Leong L,
Liu B-Q,
Diaz-Gonzalez F,
Ginsberg MH:
3 integrin-mediated fibrin clot retraction by nucleated cells: Differing behavior of IIb3 and v3.
Blood
86:2606,
1995[Abstract/Free Full Text]
140.
Schoenwaelder SM,
Yuan YP,
Cooray P,
Salem HH,
Jackson SP:
Calpain cleavage of focal adhesion proteins regulates the cytoskeletal attachment of integrin IIb3 (platelet glycoprotein IIb/IIIa) and the cellular retraction of fibrin clots.
J Biol Chem
272:1694,
1997[Abstract/Free Full Text]
141.
Fox JEB,
Reynolds CC,
Austin CD:
The role of calpain in stimulus-response coupling: Evidence that calpain mediates agonist-induced expression of procoagulant activity in platelets.
Blood
76:2510,
1990[Abstract/Free Full Text]
142. Narumiya S: The small GTPase Rho: Cellular functions and signal
transduction. J Biochem (Tokyo) 120:215, 1996
143.
Hartwig JH:
Mechanisms of actin rearrangements mediating platelet activation.
J Cell Biol
118:1421,
1992[Abstract/Free Full Text]
144.
Fox JEB:
The platelet cytoskeleton.
Thromb Haemost
70:884,
1993[Medline]
[Order article via Infotrieve]
145.
Shattil SJ,
Ginsberg MH,
Brugge JS:
Adhesive signaling in platelets.
Curr Opin Cell Biol
6:695,
1994[Medline]
[Order article via Infotrieve]
146.
Yuan YP,
Dopheide SM,
Ivanidis C,
Salem HH,
Jackson SP:
Calpain regulation of cytoskeletal signaling complexes in von Willebrand factor-stimulated plateletsDistinct roles for glycoprotein Ib-V-IX and glycoprotein IIb-IIIa (integrin IIb3) in von Willebrand factor-induced signal transduction.
J Biol Chem
272:21847,
1997[Abstract/Free Full Text]
147.
Gao J,
Zoller K,
Ginsberg MH,
Brugge JS,
Shattil SJ:
Regulation of the pp72Syk protein tyrosine kinase by platelet integrin IIb3.
EMBO J
16:6414,
1997[Medline]
[Order article via Infotrieve]
148.
Nachmias VT,
Golla R:
Vinculin in relation to stress fibers in spread platelets.
Cell Motil Cytoskeleton
20:190,
1991[Medline]
[Order article via Infotrieve]
149.
Laffargue M,
Monnereau L,
Tuech J,
Ragab A,
Ragab-Thomas J,
Payrastre B,
Raynal P,
Chap H:
Integrin-dependent tyrosine phosphorylation and cytoskeletal translocation of Tec in thrombin-activated platelets.
Biochem Biophys Res Commun
238:247,
1997[Medline]
[Order article via Infotrieve]
150.
Frangione JV,
Oda A,
Smith M,
Salzman EW,
Neel BG:
Calpain-catalyzed cleavage and subcellular relocation of protein phosphotyrosine phosphatase 1B (PTP-1B) in human platelets.
EMBO J
12:4843,
1993[Medline]
[Order article via Infotrieve]
151.
Ezumi Y,
Takayama H,
Okuma M:
Differential regulation of protein-tyrosine phosphatases by integrin IIb3 through cytoskeletal reorganization and tyrosine phosphorylation in human platelets.
J Biol Chem
270:11927,
1995[Abstract/Free Full Text]
152.
Li RY,
Ragab A,
Gaits F,
Ragab-Thomas JMF,
Chap H:
Thrombin-induced redistribution of protein-tyrosine-phosphatases to the cytoskeletal complexes in human platelets.
Cell Mol Biol
40:665,
1994
153.
Parsons JT:
Integrin-mediated signalling: Regulation by protein tyrosine kinases and small GTP-binding proteins.
Curr Opin Cell Biol
8:146,
1996[Medline]
[Order article via Infotrieve]
154.
Ilic D,
Furuta Y,
Kanazawa S,
Takeda N,
Sobue K,
Nakatsuji N,
Nomura S,
Fujimoto J,
Okada M,
Yamamoto T,
Aizawa S:
Reduced cell motility and enhanced focal adhesion formation in cells from FAK-deficient mice.
Nature
377:539,
1995[Medline]
[Order article via Infotrieve]
155.
Shattil SJ,
Haimovich B,
Cunningham M,
Lipfert L,
Parsons JT,
Ginsberg MH,
Brugge JS:
Tyrosine phosphorylation of pp125FAK in platelets requires coordinated signaling through integrin and agonist receptors.
J Biol Chem
269:14738,
1994[Abstract/Free Full Text]
156.
Leong L,
Hughes PE,
Schwartz MA,
Ginsberg MH,
Shattil SJ:
Integrin signaling: Roles for the cytoplasmic tails of IIb3 in the tyrosine phosphorylation of pp125FAK.
J Cell Sci
108:3817,
1995[Abstract]
157.
Guinebault C,
Payrastre B,
Racaud-Sultan C,
Mazarguil H,
Breton M,
Mauco G,
Plantavid M,
Chap H:
Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves specific interactions of p85- with actin filaments and focal adhesion kinase.
J Cell Biol
129:831,
1995[Abstract/Free Full Text]
158.
Hinchliffe KA,
Irvine RF,
Divecha N:
Aggregation-dependent, integrin-mediated increases in cytoskeletally associated PtdInsP2 (4,5) levels in human platelets are controlled by translocation of PtdIns 4-P 5-kinase C to the cytoskeleton.
EMBO J
15:6516,
1996[Medline]
[Order article via Infotrieve]
159.
Toyoda H,
Nakai K,
Omay SB,
Shima H,
Nagao M,
Shiku H,
Nishikawa M:
Differential association of protein Ser/Thr phosphatase types 1 and 2A with the cytoskeleton upon platelet activation.
Thromb Haemost
76:1053,
1996[Medline]
[Order article via Infotrieve]
160.
Dash D,
Aepfelbacher M,
Siess W:
Integrin IIb3-mediated translocation of CDC42Hs to the cytoskeleton in stimulated human platelets.
J Biol Chem
270:17321,
1995[Abstract/Free Full Text]
161.
Gironcel D,
Racaud-Sultan C,
Payrastre B,
Haricot M,
Borchert G,
Kieffer N,
Breton M,
Chap H:
IIb3-integrin mediated adhesion of human platelets to a fibrinogen matrix triggers phospholipase C activation and phosphatidylinositol 3 ,4-bisphosphate accumulation.
FEBS Lett
389:253,
1996[Medline]
[Order article via Infotrieve]
162.
Michelson AD:
Flow cytometry: A clinical test of platelet function.
Blood
87:4925,
1996[Free Full Text]
163.
Ginsberg MH,
Frelinger AL,
Lam SC-T,
Forsyth J,
McMillan R,
Plow EF,
Shattil SJ:
Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein IIb-IIIa with conformation-specific monoclonal antibodies.
Blood
76:2017,
1990[Abstract/Free Full Text]
164.
Gabbeta J,
Yang X,
Sun L,
McLane MA,
Niewiarowski S,
Rao AK:
Abnormal inside-out signal transduction-dependent activation of glycoprotein IIb-IIIa in a patient with impaired pleckstrin phosphorylation.
Blood
87:1368,
1996[Abstract/Free Full Text]
165.
Gabbeta J,
Yang X,
Kowalska MA,
Sun L,
Dhanasekaran N,
Rao AK:
Platelet signal transduction defect with G subunit dysfunction and diminished Gq in a patient with abnormal platelet responses.
Proc Natl Acad Sci USA
94:8750,
1997[Abstract/Free Full Text]
166.
Nurden P,
Savi P,
Heilmann E,
Bihour C,
Herbert J-M,
Maffrand J-P,
Nurden A:
An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. Its influence on glycoprotein IIb-IIIa complex function.
J Clin Invest
95:1612,
1995
167.
Lages B,
Shattil SJ,
Bainton DF,
Weiss HJ:
Decreased content and surface expression of -granule membrane protein GMP-140 in one of two types of platelet  storage pool deficiency.
J Clin Invest
87:919,
1991
168.
Lages B,
Sussman II,
Levine SP,
Coletti D,
Weiss HJ:
Platelet alpha granule deficiency associated with decreased P-selectin and selective impairment of thrombin-induced activation in a new patient with gray platelet syndrome (-storage pool deficiency).
J Lab Clin Med
129:364,
1997[Medline]
[Order article via Infotrieve]
169.
Lefkovits J,
Plow EF,
Topol EJ:
Mechanisms of disease: Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine.
N Engl J Med
332:1553,
1995[Free Full Text]
170.
Coller BS:
Platelet GPIIb/IIIa antagonists: The first anti-integrin receptor therapeutics.
J Clin Invest
99:1467,
1997[Medline]
[Order article via Infotrieve]
171. (suppl 4)
Nurden AT:
New thoughts on strategies for modulating platelet function through the inhibition of surface receptors.
Haemostasis
26:78,
1996
172.
Chothia C,
Jones EY:
The molecular structure of cell adhesion molecules.
Annu Rev Biochem
66:823,
1997[Medline]
[Order article via Infotrieve]
173.
Coppolino M,
Leung-Hagesteijn C,
Dedhar S,
Wilkins J:
Inducible interaction of integrin 21 with calreticulinDependence on the activation state of the integrin.
J Biol Chem
270:23132,
1995[Abstract/Free Full Text]
174.
Opas M,
Szewczenko-Pawlikowski M,
Jass GJ,
Mesaeli N,
Michalak M:
Calreticulin modulates cell adhesiveness via regulation of vinculin expression.
J Cell Biol
135:1913,
1996[Abstract/Free Full Text]
175.
Zhu Q,
Zelinka P,
White T,
Tanzer ML:
Calreticulin-integrin bidirectional signaling complex.
Biochem Biophys Res Commun
232:354,
1997[Medline]
[Order article via Infotrieve]
176.
Coppolino MG,
Woodside MJ,
Demaurex N,
Grinstein S,
St-Arnaud R,
Dedhar S:
Calreticulin is essential for integrin-mediated calcium signalling and cell adhesion.
Nature
386:843,
1997[Medline]
[Order article via Infotrieve]
177.
Kieffer JD,
Plopper G,
Ingber DE,
Hartwig JH,
Kupper TS:
Direct binding of F actin to the cytoplasmic domain of the 2 integrin chain in vitro.
Biochem Biophys Res Commun
217:466,
1995[Medline]
[Order article via Infotrieve]
178.
Naik UP,
Patel PM,
Parise LV:
Identification of a novel calcium binding protein that interacts with the integrin IIb cytoplasmic domain.
J Biol Chem
272:4651,
1997[Abstract/Free Full Text]
179.
Horwitz A,
Duggan K,
Buck C,
Beckerle MC,
Burridge K:
Interaction of plasma membrane fibronectin receptor with talinA transmembrane linkage.
Nature
320:531,
1986[Medline]
[Order article via Infotrieve]
180.
Knezevic I,
Leisner TM,
Lam SCT:
Direct binding of the platelet integrin IIb3 (GPIIb-IIIa) to talinEvidence that interaction is mediated through the cytoplasmic domains of both IIb and 3.
J Biol Chem
271:16416,
1996[Abstract/Free Full Text]
181.
Otey CA,
Vasquez GB,
Burridge K,
Erickson BW:
Mapping of the -actinin binding site within the 1 integrin cytoplasmic domain.
J Biol Chem
268:21193,
1993[Abstract/Free Full Text]
182. Reddy KB, Gascard P, Price MG, Fox JE: Identification and
characterization of a specific interaction between skelemin and beta
integrin cytoplasmic tails. Circ 94:I-98, 1996 (abstr)
183.
Schaller MD,
Otey CA,
Hildebrand JD,
Parsons JT:
Focal adhesion kinase and paxillin bind to peptides mimicking integrin cytoplasmic domains.
J Cell Biol
130:1181,
1995[Abstract/Free Full Text]
184.
Hannigan GE,
Leung-Hagesteijn C,
Fitz-Gibbon L,
Coppolino MG,
Radeva G,
Filmus J,
Bell JC,
Dedhar S:
Regulation of cell adhesion and anchorage-dependent growth by a new 1-integrin-linked protein kinase.
Nature
379:91,
1996[Medline]
[Order article via Infotrieve]
185.
Tanaka T,
Yamaguchi R,
Sabe H,
Sekiguchi K,
Healy JM:
Paxillin association in-vitro with integrin cytoplasmic domain peptides.
FEBS Lett
399:53,
1996[Medline]
[Order article via Infotrieve]
186.
Chang DD,
Wong C,
Smith H,
Liu J:
ICAP-1, a novel beta1 integrin cytoplasmic domain-associated protein, binds to a conserved and functionally important NPXY sequence motif of beta1 integrin.
J Cell Biol
138:1149,
1997[Abstract/Free Full Text]
187.
Sharma CP,
Ezzell RM,
Arnaout MA:
Direct interaction of filamin (ABP-280) with the 2-integrin subunit CD18.
J Immunol
154:3461,
1995[Abstract]
188.
Biffo S,
Sanvito F,
Costa S,
Preve L,
Pignatelli R,
Spinardi L,
Marchisio PC:
Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells.
J Biol Chem
272:30314,
1997[Abstract/Free Full Text]
189.
Shattil SJ,
Ginsberg MH:
Integrin signaling in vascular biology.
J Clin Invest
100:1,
1997[Medline]
[Order article via Infotrieve]
190. (abstr)
Lindberg F,
Brown EJ:
Cloning and expression of the integrin associated protein (IAP), an integral membrane protein involved in integrin signaling.
Mol Biol Cell
3:95a,
1992
191.
Berditchevski F,
Bazzoni F,
Hemler ME:
Specific association of CD63 with the VLA-3 and VLA-6 integrins.
J Biol Chem
270:17784,
1995[Abstract/Free Full Text]
192.
Berditchevski F,
Zutter MM,
Hemler ME:
Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins).
Mol Biol Cell
7:193,
1996[Abstract]
193.
Sincock PM,
Mayrhofer G,
Ashman LK:
Localization of the transmembrane 4 superfamily (TM4SF) member PETA-3 (CD151) in normal human tissues: Comparison with CD9, CD63, and alpha5beta1 integrin.
J Histochem Cytochem
45:515,
1997[Abstract/Free Full Text]
194. Maecker HT, Todd SC, Levy S: The tetraspanin superfamily:
Molecular facilitators. FASEB J 11:428, 1997
195.
Tachibana I,
Bodorova J,
Berditchevski F,
Zutter MM,
Hemler ME:
NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins.
J Biol Chem
272:29181,
1997[Abstract/Free Full Text]
196.
Berditchevski F,
Chang S,
Bodorova J,
Hemler ME:
Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with emmprin/basigin/ox47/m6.
J Biol Chem
272:29174,
1997[Abstract/Free Full Text]
197.
Wei Y,
Lukashev M,
Simon DI,
Bodary SC,
Rosenberg S,
Doyle MV,
Chapman HA:
Regulation of integrin function by the urokinase receptor.
Science
273:1551,
1996[Abstract]
198.
Xue W,
Kindzelskii AL,
Todd RF,
Petty HR:
Physical association of complement receptor type 3 and urokinase-type plasminogen activator receptor in neutrophil membranes.
J Immunol
152:4630,
1994[Abstract]
199.
Xue W,
Mizukami I,
Todd RF III,
Petty HR:
Urokinase-type plasminogen activator receptors associate with 1 and 3 integrins of fibrosarcoma cells: Dependence on extracellular matrix components.
Cancer Res
57:1682,
1997[Abstract/Free Full Text]
200.
Giurato S,
Payrastre B,
Drayer AL,
Plantavid M,
Woscholski R,
Parker P,
Erneux C,
Chap H:
Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in the thrombin-stimulated human platelets.
J Biol Chem
272:26857,
1997[Abstract/Free Full Text]
201.
Fujita A,
Saito Y,
Ishizaki T,
Maekawa M,
Fujisawa K,
Ushikabi F,
Narumiya S:
Integrin-dependent translocation of p160ROCK to cytoskeletal complex in thrombin-stimulated human platelets.
Biochem J
328:769,
1997
202.
Lilienthal J,
Chang DD:
Rak1, a receptor for activated protein kinase C, interacts with integrin subunit.
J Biol Chem
273:2379,
1998[Abstract/Free Full Text]
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M.-C. Chen, C.-F. Lin, H.-Y. Lei, S.-C. Lin, H.-S. Liu, T.-M. Yeh, R. Anderson, and Y.-S. Lin
Deletion of the C-Terminal Region of Dengue Virus Nonstructural Protein 1 (NS1) Abolishes Anti-NS1-Mediated Platelet Dysfunction and Bleeding Tendency
J. Immunol.,
August 1, 2009;
183(3):
1797 - 1803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. S. Bynagari, B. Nagy Jr., F. Tuluc, K. Bhavaraju, S. Kim, K. V. Vijayan, and S. P. Kunapuli
Mechanism of Activation and Functional Role of Protein Kinase C{eta} in Human Platelets
J. Biol. Chem.,
May 15, 2009;
284(20):
13413 - 13421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. D. Papamichael, E. M. Stathopoulou, V. D. Roussa, L. D. Tsironis, A. P. Kotsia, R.-M. Stanica, V. Moussis, V. Tsikaris, C. S. Katsouras, A. D. Tselepis, et al.
Effect of a Synthetic Peptide Corresponding to Residues 313 to 320 of the {alpha}IIb Subunit of the Human Platelet Integrin {alpha}IIb{beta}3 on Carotid Artery Thrombosis in Rabbits
J. Pharmacol. Exp. Ther.,
May 1, 2009;
329(2):
634 - 640.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kannan and R. Saxena
Glanzmann's Thrombasthenia: An Overview
Clinical and Applied Thrombosis/Hemostasis,
April 1, 2009;
15(2):
152 - 165.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. Cui, C. Chen, T. Xu, J. Zhang, X. Shang, J. Luo, L. Chen, X. Ba, and X. Zeng
c-Abl Kinase Is Required for {beta}2 Integrin-Mediated Neutrophil Adhesion
J. Immunol.,
March 1, 2009;
182(5):
3233 - 3242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. T. Newsome, R. S. Weller, J. C. Gerancher, M. A. Kutcher, and R. L. Royster
Coronary Artery Stents: II. Perioperative Considerations and Management
Anesth. Analg.,
August 1, 2008;
107(2):
570 - 590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Su, J. Mi, J. Yan, P. Flevaris, Y. Lu, H. Liu, Z. Ruan, X. Wang, N. Kieffer, S. Chen, et al.
RGT, a synthetic peptide corresponding to the integrin {beta}3 cytoplasmic C-terminal sequence, selectively inhibits outside-in signaling in human platelets by disrupting the interaction of integrin {alpha}IIb{beta}3 with Src kinase
Blood,
August 1, 2008;
112(3):
592 - 602.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Mor-Cohen, N. Rosenberg, M. Landau, J. Lahav, and U. Seligsohn
Specific Cysteines in {beta}3 Are Involved in Disulfide Bond Exchange-dependent and -independent Activation of {alpha}IIb{beta}3
J. Biol. Chem.,
July 11, 2008;
283(28):
19235 - 19244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Ghevaert, A. Salsmann, N. A. Watkins, E. Schaffner-Reckinger, A. Rankin, S. F. Garner, J. Stephens, G. A. Smith, N. Debili, W. Vainchenker, et al.
A nonsynonymous SNP in the ITGB3 gene disrupts the conserved membrane-proximal cytoplasmic salt bridge in the {alpha}IIb{beta}3 integrin and cosegregates dominantly with abnormal proplatelet formation and macrothrombocytopenia
Blood,
April 1, 2008;
111(7):
3407 - 3414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bouaouina, Y. Lad, and D. A. Calderwood
The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate {beta}1 and {beta}3 Integrins
J. Biol. Chem.,
March 7, 2008;
283(10):
6118 - 6125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Varga-Szabo, I. Pleines, and B. Nieswandt
Cell Adhesion Mechanisms in Platelets
Arterioscler Thromb Vasc Biol,
March 1, 2008;
28(3):
403 - 412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Jones, K. L. Tucker, T. Sage, W. J. Kaiser, N. E. Barrett, P. J. Lowry, A. Zimmer, S. P. Hunt, M. Emerson, and J. M. Gibbins
Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation
Blood,
January 15, 2008;
111(2):
605 - 612.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Nieswandt, M. Moser, I. Pleines, D. Varga-Szabo, S. Monkley, D. Critchley, and R. Fassler
Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo
J. Exp. Med.,
December 24, 2007;
204(13):
3113 - 3118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gundewar, J. W. Calvert, J. W. Elrod, and D. J. Lefer
Cytoprotective effects of N,N,N-trimethylsphingosine during ischemia- reperfusion injury are lost in the setting of obesity and diabetes
Am J Physiol Heart Circ Physiol,
October 1, 2007;
293(4):
H2462 - H2471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-L. Lee, M.-J. Wang, P.-R. Sudhir, G.-D. Chen, C.-W. Chi, and J.-Y. Chen
Osteopontin Promotes Integrin Activation through Outside-In and Inside-Out Mechanisms: OPN-CD44V Interaction Enhances Survival in Gastrointestinal Cancer Cells
Cancer Res.,
March 1, 2007;
67(5):
2089 - 2097.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. R. Van de Walle, A. Schoolmeester, B. F. Iserbyt, J. M. E. M. Cosemans, J. W. M. Heemskerk, M. F. Hoylaerts, A. Nurden, K. Vanhoorelbeke, and H. Deckmyn
Activation of {alpha}IIb{beta}3 is a sufficient but also an imperative prerequisite for activation of {alpha}2{beta}1 on platelets
Blood,
January 15, 2007;
109(2):
595 - 602.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Hyduk, J. R. Chan,, S. T. Duffy, M. Chen, M. D. Peterson, T. K. Waddell, G. C. Digby, K. Szaszi, A. Kapus, and M. I. Cybulsky
Phospholipase C, calcium, and calmodulin are critical for {alpha}4{beta}1 integrin affinity up-regulation and monocyte arrest triggered by chemoattractants
Blood,
January 1, 2007;
109(1):
176 - 184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yin, R. I. Litvinov, G. Vilaire, H. Zhu, W. Li, G. A. Caputo, D. T. Moore, J. D. Lear, J. W. Weisel, W. F. DeGrado, et al.
Activation of Platelet {alpha}IIbbeta3 by an Exogenous Peptide Corresponding to the Transmembrane Domain of {alpha}IIb
J. Biol. Chem.,
December 1, 2006;
281(48):
36732 - 36741.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Lad, B. McHugh, P. S. Hodkinson, A. C. MacKinnon, C. Haslett, M. H. Ginsberg, and T. Sethi
Phospholipase C{epsilon} Suppresses Integrin Activation
J. Biol. Chem.,
October 6, 2006;
281(40):
29501 - 29512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Xi, P. Flevaris, A. Stojanovic, A. Chishti, D. R. Phillips, S. C. T. Lam, and X. Du
Tyrosine Phosphorylation of the Integrin beta3 Subunit Regulates beta3 Cleavage by Calpain
J. Biol. Chem.,
October 6, 2006;
281(40):
29426 - 29430.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Akar, M. A. Ozcan, H. Ates, O. Gurler, I. Alacacioglu, G. H. Ozsan, N. Akkoc, S. Ozkan, F. Demirkan, and F. Onen
Circulated Activated Platelets and Increased Platelet Reactivity in Patients With Behcet's Disease
Clinical and Applied Thrombosis/Hemostasis,
October 1, 2006;
12(4):
451 - 457.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W.-Y. Wang, Y.-C. Wu, and C.-C. Wu
Prevention of Platelet Glycoprotein IIb/IIIa Activation by 3,4-Methylenedioxy-beta-Nitrostyrene, A Novel Tyrosine Kinase Inhibitor
Mol. Pharmacol.,
October 1, 2006;
70(4):
1380 - 1389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. O'Kennedy, L. Crosbie, M. van Lieshout, J. I Broom, D. J Webb, and A. K Duttaroy
Effects of antiplatelet components of tomato extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans.
Am. J. Clinical Nutrition,
September 1, 2006;
84(3):
570 - 579.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gao, Y. Feng, R. Bowers, M. Becker-Hapak, J. Gardner, L. Council, G. Linette, H. Zhao, and L. A. Cornelius
Ras-Associated Protein-1 Regulates Extracellular Signal-Regulated Kinase Activation and Migration in Melanoma Cells: Two Processes Important to Melanoma Tumorigenesis and Metastasis
Cancer Res.,
August 15, 2006;
66(16):
7880 - 7888.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Stojanovic, J. A. Marjanovic, V. M. Brovkovych, X. Peng, N. Hay, R. A. Skidgel, and X. Du
A Phosphoinositide 3-Kinase-AKT-Nitric Oxide-cGMP Signaling Pathway in Stimulating Platelet Secretion and Aggregation
J. Biol. Chem.,
June 16, 2006;
281(24):
16333 - 16339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Medina, P. Jurasz, M. J. Santos-Martinez, S. S. Jeong, T. Mitsky, R. Chen, and M. W. Radomski
Platelet Aggregation-Induced by Caco-2 Cells: Regulation by Matrix Metalloproteinase-2 and Adenosine Diphosphate
J. Pharmacol. Exp. Ther.,
May 1, 2006;
317(2):
739 - 745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Li, G. Zhang, R. Feil, J. Han, and X. Du
Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin {alpha}IIbbeta3
Blood,
February 1, 2006;
107(3):
965 - 972.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Staelens, M. A. Hadders, S. Vauterin, C. Platteau, M. De Maeyer, K. Vanhoorelbeke, E. G. Huizinga, and H. Deckmyn
Paratope Determination of the Antithrombotic Antibody 82D6A3 Based on the Crystal Structure of Its Complex with the von Willebrand Factor A3-Domain
J. Biol. Chem.,
January 27, 2006;
281(4):
2225 - 2231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Garcia, T. M. Quinton, R. T. Dorsam, and S. P. Kunapuli
Src family kinase-mediated and Erk-mediated thromboxane A2 generation are essential for VWF/GPIb-induced fibrinogen receptor activation in human platelets
Blood,
November 15, 2005;
106(10):
3410 - 3414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Marjanovic, Z. Li, A. Stojanovic, and X. Du
Stimulatory Roles of Nitric-oxide Synthase 3 and Guanylyl Cyclase in Platelet Activation
J. Biol. Chem.,
November 11, 2005;
280(45):
37430 - 37438.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. S. Stork and T. J. Dillon
Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions
Blood,
November 1, 2005;
106(9):
2952 - 2961.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Y. Maeda, S. P. Bydlowski, and A. A. Lopes
Increased Tyrosine Phosphorylation of Platelet Proteins Including pp125FAK Suggests Endogenous Activation and Aggregation in Pulmonary Hypertension
Clinical and Applied Thrombosis/Hemostasis,
October 1, 2005;
11(4):
411 - 415.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Kessler, R. Bieker, T. Padro, C. Schwoppe, T. Persigehl, C. Bremer, M. Kreuter, W. E. Berdel, and R. M. Mesters
Inhibition of Tumor Growth by RGD Peptide-Directed Delivery of Truncated Tissue Factor to the Tumor Vasculature
Clin. Cancer Res.,
September 1, 2005;
11(17):
6317 - 6324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kashiwagi, M. Shiraga, H. Kato, T. Kamae, N. Yamamoto, S. Tadokoro, Y. Kurata, Y. Tomiyama, and Y. Kanakura
Negative regulation of platelet function by a secreted cell repulsive protein, semaphorin 3A
Blood,
August 1, 2005;
106(3):
913 - 921.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Murugappan, H. Shankar, S. Bhamidipati, R. T. Dorsam, J. Jin, and S. P. Kunapuli
Molecular mechanism and functional implications of thrombin-mediated tyrosine phosphorylation of PKC{delta} in platelets
Blood,
July 15, 2005;
106(2):
550 - 557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Liu, C. W. Jackson, R. A. Gruppo, L. K. Jennings, and T. K. Gartner
The {beta}3 subunit of the integrin {alpha}IIb{beta}3 regulates {alpha}IIb-mediated outside-in signaling
Blood,
June 1, 2005;
105(11):
4345 - 4352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Jordan, J. M. Stevens, G. P. Hubbard, N. E. Barrett, T. Sage, K. S. Authi, and J. M. Gibbins
A role for the thiol isomerase protein ERP5 in platelet function
Blood,
February 15, 2005;
105(4):
1500 - 1507.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Hetherington, R. K. Singh, D. Lodwick, J. R. Thompson, A. H. Goodall, and N. J. Samani
Dimorphism in the P2Y1 ADP Receptor Gene Is Associated With Increased Platelet Activation Response to ADP
Arterioscler Thromb Vasc Biol,
January 1, 2005;
25(1):
252 - 257.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Litvinov, C. Nagaswami, G. Vilaire, H. Shuman, J. S. Bennett, and J. W. Weisel
Functional and structural correlations of individual {alpha}IIb{beta}3 molecules
Blood,
December 15, 2004;
104(13):
3979 - 3985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Li, G. Zhang, J. A. Marjanovic, C. Ruan, and X. Du
A Platelet Secretion Pathway Mediated by cGMP-dependent Protein Kinase
J. Biol. Chem.,
October 8, 2004;
279(41):
42469 - 42475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-L. Huang, J.-C. Cheng, C.-H. Liao, A. Stern, J.-T. Hsieh, C.-H. Wang, H.-L. Hsu, and C.-P. Tseng
Disabled-2 Is a Negative Regulator of Integrin {alpha}IIb{beta}3-mediated Fibrinogen Adhesion and Cell Signaling
J. Biol. Chem.,
October 1, 2004;
279(40):
42279 - 42289.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lecut, A. Schoolmeester, M. J.E. Kuijpers, J. L.V. Broers, M. A.M.J. van Zandvoort, K. Vanhoorelbeke, H. Deckmyn, M. Jandrot-Perrus, and J. W.M. Heemskerk
Principal Role of Glycoprotein VI in {alpha}2{beta}1 and {alpha}IIb{beta}3 Activation During Collagen-Induced Thrombus Formation
Arterioscler Thromb Vasc Biol,
September 1, 2004;
24(9):
1727 - 1733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. W. Kerrigan, M. Gaur, R. P. Murphy, S. J. Shattil, and A. D. Leavitt
Caspase-12: a developmental link between G-protein-coupled receptors and integrin {alpha}IIb{beta}3 activation
Blood,
September 1, 2004;
104(5):
1327 - 1334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S Ross
Molecular and mechanical synergy: cross-talk between integrins and growth factor receptors
Cardiovasc Res,
August 15, 2004;
63(3):
381 - 390.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. V. Vijayan, Y. Liu, T.-T. Li, and P. F. Bray
Protein Phosphatase 1 Associates with the Integrin {alpha}IIb Subunit and Regulates Signaling
J. Biol. Chem.,
August 6, 2004;
279(32):
33039 - 33042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Maxwell, Y. Yuan, K. E. Anderson, M. L. Hibbs, H. H. Salem, and S. P. Jackson
SHIP1 and Lyn Kinase Negatively Regulate Integrin {alpha}IIb{beta}3 Signaling in Platelets
J. Biol. Chem.,
July 30, 2004;
279(31):
32196 - 32204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Gibbins
Platelet adhesion signalling and the regulation of thrombus formation
J. Cell Sci.,
July 15, 2004;
117(16):
3415 - 3425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. de Virgilio, W. B. Kiosses, and S. J. Shattil
Proximal, selective, and dynamic interactions between integrin {alpha}IIb{beta}3 and protein tyrosine kinases in living cells
J. Cell Biol.,
May 10, 2004;
165(3):
305 - 311.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kasirer-Friede, M. R. Cozzi, M. Mazzucato, L. De Marco, Z. M. Ruggeri, and S. J. Shattil
Signaling through GP Ib-IX-V activates {alpha}IIb{beta}3 independently of other receptors
Blood,
May 1, 2004;
103(9):
3403 - 3411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Schwarz, Y. Katagiri, M. Kotani, N. Bassler, C. Loeffler, C. Bode, and K. Peter
Reversibility versus Persistence of GPIIb/IIIa Blocker-Induced Conformational Change of GPIIb/IIIa ({alpha}IIb{beta}3, CD41/CD61)
J. Pharmacol. Exp. Ther.,
March 1, 2004;
308(3):
1002 - 1011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Sun, G. Mao, and A. K. Rao
Association of CBFA2 mutation with decreased platelet PKC-{theta} and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation
Blood,
February 1, 2004;
103(3):
948 - 954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Litvinov, G. Vilaire, H. Shuman, J. S. Bennett, and J. W. Weisel
Quantitative Analysis of Platelet {alpha}v{beta}3 Binding to Osteopontin Using Laser Tweezers
J. Biol. Chem.,
December 19, 2003;
278(51):
51285 - 51290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gruner, M. Prostredna, V. Schulte, T. Krieg, B. Eckes, C. Brakebusch, and B. Nieswandt
Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo
Blood,
December 1, 2003;
102(12):
4021 - 4027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. U. Naik and U. P. Naik
Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen
Blood,
November 15, 2003;
102(10):
3629 - 3636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G.A. Stouffer and S.S. Smyth
Effects of Thrombin on Interactions Between {beta}3-Integrins and Extracellular Matrix in Platelets and Vascular Cells
Arterioscler Thromb Vasc Biol,
November 1, 2003;
23(11):
1971 - 1978.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Butta, E. G. Arias-Salgado, C. Gonzalez-Manchon, M. Ferrer, S. Larrucea, M. S. Ayuso, and R. Parrilla
Disruption of the {beta}3 663-687 disulfide bridge confers constitutive activity to {beta}3 integrins
Blood,
October 1, 2003;
102(7):
2491 - 2497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Macchi, L. Christiaens, S. Brabant, N. Sorel, S. Ragot, J. Allal, G. Mauco, and A. Brizard
Resistance in vitro to low-dose aspirin is associated with platelet PlA1 (GP IIIa) polymorphism but not with C807T(GP Ia/IIa) and C-5T kozak (GP Ib{alpha}) polymorphisms
J. Am. Coll. Cardiol.,
September 17, 2003;
42(6):
1115 - 1119.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ferkowicz, M. Starr, X. Xie, W. Li, S. A. Johnson, W. C. Shelley, P. R. Morrison, and M. C. Yoder
CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo
Development,
September 15, 2003;
130(18):
4393 - 4403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lahav, E. M. Wijnen, O. Hess, S. W. Hamaia, D. Griffiths, M. Makris, C. G. Knight, D. W. Essex, and R. W. Farndale
Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin {alpha}2{beta}1
Blood,
September 15, 2003;
102(6):
2085 - 2092.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Goncalves, S. C. Hughan, S. M. Schoenwaelder, C. L. Yap, Y. Yuan, and S. P. Jackson
Integrin {alpha}IIb{beta}3-dependent Calcium Signals Regulate Platelet-Fibrinogen Interactions under Flow: INVOLVEMENT OF PHOSPHOLIPASE C{gamma}2
J. Biol. Chem.,
September 12, 2003;
278(37):
34812 - 34822.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. P. Naik and M. U. Naik
Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen
Blood,
August 15, 2003;
102(4):
1355 - 1362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Xi, R. J. Bodnar, Z. Li, S. C.-T. Lam, and X. Du
Critical roles for the COOH-terminal NITY and RGT sequences of the integrin {beta}3 cytoplasmic domain in inside-out and outside-in signaling
J. Cell Biol.,
July 21, 2003;
162(2):
329 - 339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-M. Xiong, J. Chen, and L. Zhang
Modulation of CD11b/CD18 Adhesive Activity by Its Extracellular, Membrane-Proximal Regions
J. Immunol.,
July 15, 2003;
171(2):
1042 - 1050.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Nieswandt and S. P. Watson
Platelet-collagen interaction: is GPVI the central receptor?
Blood,
July 15, 2003;
102(2):
449 - 461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tabuchi, A. Yoshioka, T. Higashi, R. Shirakawa, H. Nishioka, T. Kita, and H. Horiuchi
Direct Demonstration of Involvement of Protein Kinase C{alpha} in the Ca2+-induced Platelet Aggregation
J. Biol. Chem.,
July 11, 2003;
278(29):
26374 - 26379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T.-T. Fujimoto, S. Katsutani, T. Shimomura, and K. Fujimura
Thrombospondin-bound Integrin-associated Protein (CD47) Physically and Functionally Modifies Integrin {alpha}IIb{beta}3 by Its Extracellular Domain
J. Biol. Chem.,
July 11, 2003;
278(29):
26655 - 26665.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Ly, K. M. Zazzali, and S. A. Corbett
De Novo Expression of the Integrin {alpha}5{beta}1 Regulates {alpha}v{beta}3-mediated Adhesion and Migration on Fibrinogen
J. Biol. Chem.,
June 6, 2003;
278(24):
21878 - 21885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Quinn, T. V. Byzova, J. Qin, E. J. Topol, and E. F. Plow
Integrin {alpha}IIb{beta}3 and Its Antagonism
Arterioscler Thromb Vasc Biol,
June 1, 2003;
23(6):
945 - 952.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Inwald, A. McDowall, M. J. Peters, R. E. Callard, and N. J. Klein
CD40 Is Constitutively Expressed on Platelets and Provides a Novel Mechanism for Platelet Activation
Circ. Res.,
May 16, 2003;
92(9):
1041 - 1048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Buensuceso, M. de Virgilio, and S. J. Shattil
Detection of Integrin alpha IIbbeta 3 Clustering in Living Cells
J. Biol. Chem.,
April 18, 2003;
278(17):
15217 - 15224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Resendiz, S. Feng, G. Ji, K. A. Francis, M. C. Berndt, and M. H. Kroll
Purinergic P2Y12 Receptor Blockade Inhibits Shear-Induced Platelet Phosphatidylinositol 3-Kinase Activation
Mol. Pharmacol.,
March 1, 2003;
63(3):
639 - 645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. R. Hantgan, D. S. Lyles, T. C. Mallett, M. Rocco, C. Nagaswami, and J. W. Weisel
Ligand Binding Promotes the Entropy-driven Oligomerization of Integrin alpha IIbbeta 3
J. Biol. Chem.,
January 24, 2003;
278(5):
3417 - 3426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sajid, K. V. Vijayan, S. Souza, and P. F. Bray
PlA Polymorphism of Integrin {beta}3 Differentially Modulates Cellular Migration on Extracellular Matrix Proteins
Arterioscler Thromb Vasc Biol,
December 1, 2002;
22(12):
1984 - 1989.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Dorsam, S. Kim, J. Jin, and S. P. Kunapuli
Coordinated Signaling through Both G12/13 and Gi Pathways Is Sufficient to Activate GPIIb/IIIa in Human Platelets
J. Biol. Chem.,
November 27, 2002;
277(49):
47588 - 47595.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Calzada, M. V. Alvarez, and J. Gonzalez-Rodriguez
Agonist-specific Structural Rearrangements of Integrin alpha IIbbeta 3. CONFIRMATION OF THE BENT CONFORMATION IN PLATELETS AT REST AND AFTER ACTIVATION
J. Biol. Chem.,
October 11, 2002;
277(42):
39899 - 39908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Eto, R. Murphy, S. W. Kerrigan, A. Bertoni, H. Stuhlmann, T. Nakano, A. D. Leavitt, and S. J. Shattil
Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling
PNAS,
October 1, 2002;
99(20):
12819 - 12824.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Szasz and G. L. Dale
Thrombospondin and fibrinogen bind serotonin-derivatized proteins on COAT-platelets
Blood,
September 26, 2002;
100(8):
2827 - 2831.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lahav, K. Jurk, O. Hess, M. J. Barnes, R. W. Farndale, J. Luboshitz, and B. E. Kehrel
Sustained integrin ligation involves extracellular free sulfhydryls and enzymatically catalyzed disulfide exchange
Blood,
September 18, 2002;
100(7):
2472 - 2478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q.-H. Sun, C.-Y. Liu, R. Wang, C. Paddock, and P. J. Newman
Disruption of the long-range GPIIIa Cys5-Cys435 disulfide bond results in the production of constitutively active GPIIb-IIIa (alpha IIbbeta 3) integrin complexes
Blood,
August 28, 2002;
100(6):
2094 - 2101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. T. Barry, C. Boudignon-Proudhon, D. D. Shock, A. McFadden, J. M. Weiss, J. Sondek, and L. V. Parise
Molecular Basis of CIB Binding to the Integrin alpha IIb Cytoplasmic Domain
J. Biol. Chem.,
August 2, 2002;
277(32):
28877 - 28883.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bertoni, S. Tadokoro, K. Eto, N. Pampori, L. V. Parise, G. C. White, and S. J. Shattil
Relationships between Rap1b, Affinity Modulation of Integrin alpha IIbbeta 3, and the Actin Cytoskeleton
J. Biol. Chem.,
July 5, 2002;
277(28):
25715 - 25721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cattaneo, C. Gachet, J.-P. Cazenave, M. A. Packham ;, J. Jin, T. M. Quinton, J. Zhang, S. E. Rittenhouse, and S. P. Kunapuli
Adenosine diphosphate (ADP) does not induce thromboxane A2 generation in human platelets
Blood,
May 15, 2002;
99(10):
3868 - 3870.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Valles, M. T. Santos, J. Aznar, M. Martinez, A. Moscardo, M. Pinon, M. J. Broekman, and A. J. Marcus
Platelet-erythrocyte interactions enhance alpha IIbbeta 3 integrin receptor activation and P-selectin expression during platelet recruitment: down-regulation by aspirin ex vivo
Blood,
May 13, 2002;
99(11):
3978 - 3984.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Obergfell, K. Eto, A. Mocsai, C. Buensuceso, S. L. Moores, J. S. Brugge, C. A. Lowell, and S. J. Shattil
Coordinate interactions of Csk, Src, and Syk kinases with {alpha}IIb{beta}3 initiate integrin signaling to the cytoskeleton
J. Cell Biol.,
April 15, 2002;
157(2):
265 - 275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Larrucea, C. Gonzalez-Manchon, N. Butta, E. G. Arias-Salgado, L. Shen, M. S. Ayuso, and R. Parrilla
Agonist-induced aggregation of Chinese hamster ovary cells coexpressing the human receptors for fibrinogen (integrin alpha IIbbeta 3) and the platelet-activating factor: dissociation between adhesion and aggregation
Blood,
April 15, 2002;
99(8):
2819 - 2827.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Luciardi, S. Berman, J. Muntaner, F. De La Serna, and R. Altman
Facilitated Thrombolysis: Dethrombosis?
Clinical and Applied Thrombosis/Hemostasis,
April 1, 2002;
8(2):
133 - 138.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Kasirer-Friede, J. Ware, L. Leng, P. Marchese, Z. M. Ruggeri, and S. J. Shattil
Lateral Clustering of Platelet GP Ib-IX Complexes Leads to Up-regulation of the Adhesive Function of Integrin alpha IIbbeta 3
J. Biol. Chem.,
March 29, 2002;
277(14):
11949 - 11956.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Haataja, V. Kaartinen, J. Groffen, and N. Heisterkamp
The Small GTPase Rac3 Interacts with the Integrin-binding Protein CIB and Promotes Integrin alpha IIbbeta 3-mediated Adhesion and Spreading
J. Biol. Chem.,
March 1, 2002;
277(10):
8321 - 8328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Iwaki, M. J. Sandoval-Cooper, M. Paiva, T. Kobayashi, V. A. Ploplis, and F. J. Castellino
Fibrinogen Stabilizes Placental-Maternal Attachment During Embryonic Development in the Mouse
Am. J. Pathol.,
March 1, 2002;
160(3):
1021 - 1034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Jin, T. M. Quinton, J. Zhang, S. E. Rittenhouse, and S. P. Kunapuli
Adenosine diphosphate (ADP)-induced thromboxane A2 generation in human platelets requires coordinated signaling through integrin alpha IIbbeta 3 and ADP receptors
Blood,
January 1, 2002;
99(1):
193 - 198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Wentzel, A. Christmann, T. Adams, and H. Kolmar
Display of Passenger Proteins on the Surface of Escherichia coli K-12 by the Enterohemorrhagic E. coli Intimin EaeA
J. Bacteriol.,
December 15, 2001;
183(24):
7273 - 7284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Li, X. Xi, and X. Du
A Mitogen-activated Protein Kinase-dependent Signaling Pathway in the Activation of Platelet Integrin alpha IIbbeta 3
J. Biol. Chem.,
November 2, 2001;
276(45):
42226 - 42232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Zunino, Q. Li, S. D. Rose, M. M. I. Romero-Benitez, T. Lejen, N. C. Brandan, and J.-M. Trifaro
Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
Blood,
October 1, 2001;
98(7):
2210 - 2219.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Rose, V. Grabovsky, R. Alon, and M. H. Ginsberg
The Affinity of Integrin {alpha}4{beta}1 Governs Lymphocyte Migration
J. Immunol.,
September 1, 2001;
167(5):
2824 - 2830.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Bouvard, C. Brakebusch, E. Gustafsson, A. Aszodi, T. Bengtsson, A. Berna, and R. Fassler
Functional Consequences of Integrin Gene Mutations in Mice
Circ. Res.,
July 30, 2001;
89(3):
211 - 223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Introduction
References
Introduction