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Role for the guanine nucleotide exchange factor phosphatidylinositol-3,4,5- trisphosphate-dependent rac exchanger 1 in platelet secretion and aggregation
Qian F.3; Le Breton G.C.3; Chen J.3; Deng J.2; Christman J.W.2; Wu D.1; Ye R.D.3
2012-03-01
Source PublicationArteriosclerosis, Thrombosis, and Vascular Biology
ISSN10795642 15244636
Volume32Issue:3Pages:768-777
AbstractObjective-Recent studies have shown a role for Rac1 in regulating platelet functions, but how Rac1 is activated in platelets remains unclear. Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchanger 1 (P-Rex1) was originally identified in neutrophils that regulates phagocyte functions. We sought to examine whether P-Rex1 plays a role in platelet activation. Methods and Results-Western blotting showed P-Rex1 expression in mouse and human platelets. Mice lacking P-Rex1 exhibited prolonged bleeding time and increased rebleeding. When challenged with low doses of the G protein-coupled receptor (GPCR) agonists U46619 and thrombin, P-Rex1 platelets displayed significantly reduced secretion and aggregation compared with wild-type platelets. Increasing the concentration of these agonists could overcome the defect. Platelet aggregation induced by collagen, a non-GPCR agonist, was also compromised in the absence of P-Rex1. Along with these phenotypic changes were impaired Rac1 activation; reduced ATP secretion; and decreased phosphorylation of Akt, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase in P-Rex1 platelets on agonist stimulation. Conclusion-These results demonstrate for the first time the presence of P-Rex1 in platelets as well as its role in platelet secretion and aggregation induced by low-dose agonists for GPCR and by collagen. © 2012 American Heart Association, Inc.
KeywordG proteins platelets receptors signal transduction thrombosis
DOI10.1161/ATVBAHA.111.243675
URLView the original
Language英語
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Cited Times [WOS]:16   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Yale University School of Medicine
2.University of Illinois College of Medicine
3.University of Illinois at Chicago
Recommended Citation
GB/T 7714
Qian F.,Le Breton G.C.,Chen J.,et al. Role for the guanine nucleotide exchange factor phosphatidylinositol-3,4,5- trisphosphate-dependent rac exchanger 1 in platelet secretion and aggregation[J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2012,32(3):768-777.
APA Qian F..,Le Breton G.C..,Chen J..,Deng J..,Christman J.W..,...&Ye R.D..(2012).Role for the guanine nucleotide exchange factor phosphatidylinositol-3,4,5- trisphosphate-dependent rac exchanger 1 in platelet secretion and aggregation.Arteriosclerosis, Thrombosis, and Vascular Biology,32(3),768-777.
MLA Qian F.,et al."Role for the guanine nucleotide exchange factor phosphatidylinositol-3,4,5- trisphosphate-dependent rac exchanger 1 in platelet secretion and aggregation".Arteriosclerosis, Thrombosis, and Vascular Biology 32.3(2012):768-777.
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