|
|
Blood, 15 November 2003, Vol. 102, No. 10, pp. 3658-3664.
Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-06-1888.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets
Vipul Rathore,
Michelle A. Stapleton,
Cheryl A. Hillery,
Robert R. Montgomery,
Timothy C. Nichols,
Elizabeth P. Merricks,
Debra K. Newman, and
Peter J. Newman
From the Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee; the Cardiovascular Center and the Departments of Pediatrics, Microbiology, Pharmacology, and Cellular Biology, Medical College of Wisconsin, Milwaukee; and the Department of Pathology and Laboratory Medicine, The School of Medicine, University of North Carolina at Chapel Hill.
Platelet adhesion at sites of vascular injury is mediated, in part, by interaction of the platelet plasma membrane glycoprotein (GP) Ib/V/IX complex with von Willebrand Factor (VWF) presented on collagen-exposed surfaces. Recent studies indicate that GPIb/V/IX may be functionally coupled with the Fc receptor  (FcR)-chain, which, by virtue of its cytoplasmic immunoreceptor tyrosine-based activation motif, sends activation signals into the cell. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an inhibitory receptor that has previously been shown to negatively regulate platelet responses to collagen, which transduces activation signals via the GPVI/FcR-chain complex. To determine whether PECAM-1 might similarly regulate signals emanating from GPIb/FcR, we compared activation and aggregation responses to VWF of PECAM-1-positive and PECAM-1-deficient murine platelets. PECAM-1 and the FcR-chain became rapidly tyrosine phosphorylated in platelets following botrocetin-induced VWF binding, but FcR-chain tyrosine phosphorylation was delayed in PECAM-1-positive, versus PECAM-1-deficient, platelets. PECAM-1-deficient platelets were hyperaggregable to VWF, exhibited enhanced spreading and, under conditions of arterial flow, formed markedly larger thrombi on immobilized VWF than did wild-type platelets. Taken together, these data support the notion that engagement of the GPIb complex, in addition to sending activation signals, also initiates a negative feedback loop involving PECAM-1 that controls the rate and extent of platelet activation. (Blood. 2003;102:3658-3664)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Bergom, C. Paddock, C. Gao, T. Holyst, D. K. Newman, and P. J. Newman
An alternatively spliced isoform of PECAM-1 is expressed at high levels in human and murine tissues, and suggests a novel role for the C-terminus of PECAM-1 in cytoprotective signaling
J. Cell Sci.,
April 15, 2008;
121(8):
1235 - 1242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Goel, B. Boylan, L. Gruman, P. J. Newman, P. E. North, and D. K. Newman
The proinflammatory phenotype of PECAM-1-deficient mice results in atherogenic diet-induced steatohepatitis
Am J Physiol Gastrointest Liver Physiol,
December 1, 2007;
293(6):
G1205 - G1214.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Andrews, D. Karunakaran, E. E. Gardiner, and M. C. Berndt
Platelet Receptor Proteolysis: A Mechanism for Downregulating Platelet Reactivity
Arterioscler. Thromb. Vasc. Biol.,
July 1, 2007;
27(7):
1511 - 1520.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. J.H. Sachs and B. Nieswandt
In Vivo Thrombus Formation in Murine Models
Circ. Res.,
April 13, 2007;
100(7):
979 - 991.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. P. Jackson, S. Cranmer, P. Mangin, and Y. Yuan
Are Erk, Btk, and PECAM-1 major players in GPIb signaling? The challenge of unraveling signaling events downstream of platelet GPIb
Blood,
January 15, 2007;
109(2):
846 - 847.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. Lee, M. van Lier, I. A. M. Relou, L. Foley, J.-W. N. Akkerman, H. F. G. Heijnen, and R. W. Farndale
Lipid Rafts Facilitate the Interaction of PECAM-1 with the Glycoprotein VI-FcR {gamma}-Chain Complex in Human Platelets
J. Biol. Chem.,
December 22, 2006;
281(51):
39330 - 39338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Pergolizzi, G. Jin, D. Chan, L. Pierre, J. Bussel, B. Ferris, P. L. Leopold, and R. G. Crystal
Correction of a murine model of von Willebrand disease by gene transfer
Blood,
August 1, 2006;
108(3):
862 - 869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Falati, S. Patil, P. L. Gross, M. Stapleton, G. Merrill-Skoloff, N. E. Barrett, K. L. Pixton, H. Weiler, B. Cooley, D. K. Newman, et al.
Platelet PECAM-1 inhibits thrombus formation in vivo
Blood,
January 15, 2006;
107(2):
535 - 541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Wee and D. E. Jackson
The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling properties of integrin {alpha}IIb{beta}3 in platelets
Blood,
December 1, 2005;
106(12):
3816 - 3823.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J.A. Korporaal, G. Gorter, H. J.M. van Rijn, and J.-W. N. Akkerman
Effect of Oxidation on the Platelet-Activating Properties of Low-Density Lipoprotein
Arterioscler. Thromb. Vasc. Biol.,
April 1, 2005;
25(4):
867 - 872.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Maas, M. Stapleton, C. Bergom, D. L. Mattson, D. K. Newman, and P. J. Newman
Endothelial cell PECAM-1 confers protection against endotoxic shock
Am J Physiol Heart Circ Physiol,
January 1, 2005;
288(1):
H159 - H164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Shattil and P. J. Newman
Integrins: dynamic scaffolds for adhesion and signaling in platelets
Blood,
September 15, 2004;
104(6):
1606 - 1615.
[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]
|
|
|
| |
