|
|
Prepublished online as a Blood First Edition Paper on December 19, 2002; DOI 10.1182/blood-2002-09-2807.
Submitted September 16, 2002
Accepted November 29, 2002
IQGAP2 functions as a GTP-dependent effector protein in thrombin-induced platelet cytoskeletal reorganization
Valentina A Schmidt, Lesley Scudder, Craig E Devoe, Andre Bernards, Lisa D Cupit, and Wadie F Bahou*
Department of Medicine, State University of New York, Stony Brook, NY, USA
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, USA
Department of Medicine, Veteran's Administration Medical Center, Northport, NY, USA
Program in Genetics, State University of New York, Stony Brook, NY, USA
* Corresponding author; email: wbahou{at}notes.cc.sunysb.edu.
Human blood platelets are anucleate cells whose response to extracellular stimuli results in actin cytoskeleton rearrangements, thereby providing the critical initial step in regulation of hemostasis. The serine protease  -thrombin -- known to activate platelets by cleavage of a family of protease activated receptors (PARs) -- is the most potent physiological activator of human platelets, although downstream effector proteins uniquely linked to platelet cytoskeletal actin polymerization remain largely uncharacterized. The gene encoding the putative rac1/cdc42 effector protein IQGAP2 was identified within the PAR gene cluster at 5q13, flanked telomeric by PAR1 and encompassing PAR3. Immunofluorescence microscopy demonstrated IQGAP2 expression in filopodial extensions of activated platelets, and co-localized with F-actin in lamellipodia and filopodia of IQGAP2-transfected COS1 cells. Platelet activation by -thrombin, but not saturating concentrations of fibrillar collagen or adenosine 5'-diphosphate, uniquely assemble an IQGAP2/arp2/3-actin cytoplasmic complex, an association regulated by [GTP]rac1, but not [GTP]cdc42. Likewise, only thrombin-activated platelets resulted in rapid translocation of IQGAP2 to the platelet cytoskeleton. These observations identify a physiological scaffolding function for IQGAP2, and establish the presence of a functional genomic unit in humans uniquely evolved to regulate thrombin-induced platelet cytoskeletal actin reorganization.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
V. A. Schmidt, C. S. Chiariello, E. Capilla, F. Miller, and W. F. Bahou
Development of Hepatocellular Carcinoma in Iqgap2-Deficient Mice Is IQGAP1 Dependent
Mol. Cell. Biol.,
March 1, 2008;
28(5):
1489 - 1502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Bensenor, H.-M. Kan, N. Wang, H. Wallrabe, L. A. Davidson, Y. Cai, D. A. Schafer, and G. S. Bloom
IQGAP1 regulates cell motility by linking growth factor signaling to actin assembly
J. Cell Sci.,
February 15, 2007;
120(4):
658 - 669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Steinhoff, J. Buddenkotte, V. Shpacovitch, A. Rattenholl, C. Moormann, N. Vergnolle, T. A. Luger, and M. D. Hollenberg
Proteinase-Activated Receptors: Transducers of Proteinase-Mediated Signaling in Inflammation and Immune Response
Endocr. Rev.,
February 1, 2005;
26(1):
1 - 43.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Chew, C. T. Okamoto, X. Chen, and H. Y. Qin
IQGAPs are differentially expressed and regulated in polarized gastric epithelial cells
Am J Physiol Gastrointest Liver Physiol,
February 1, 2005;
288(2):
G376 - G387.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. F. Bahou, L. Scudder, D. Rubenstein, and J. Jesty
A Shear-restricted Pathway of Platelet Procoagulant Activity Is Regulated by IQGAP1
J. Biol. Chem.,
May 21, 2004;
279(21):
22571 - 22577.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
