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Prepublished online as a Blood First Edition Paper on December 19, 2002; DOI 10.1182/blood-2002-09-2807.
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Blood, 15 April 2003, Vol. 101, No. 8, pp. 3021-3028
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
IQGAP2 functions as a GTP-dependent effector protein in
thrombin-induced platelet cytoskeletal reorganization
Valentina A. Schmidt,
Lesley Scudder,
Craig E. Devoe,
André Bernards,
Lisa D. Cupit, and
Wadie F. Bahou
From the Department of Medicine and the Program in
Genetics, State University of New York, Stony Brook; the Massachusetts
General Hospital Cancer Center, Harvard Medical School, Charlestown;
and the Department of Medicine, Veteran's Administration Medical
Center, Northport, NY.
Human blood platelets are anucleate cells whose response to
extracellular stimuli results in actin cytoskeleton rearrangements, thereby providing the critical initial step in the 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 physiologic activator of human platelets, though 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 colocalized 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 guanosine triphosphate
rac1 ([GTP]rac1) but not by [GTP]cdc42. Likewise, only
thrombin-activated platelets resulted in rapid translocation of IQGAP2
to the platelet cytoskeleton. These observations identify a physiologic
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.
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