| First Author | Qian F | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 3 | Pages | 768-77 |
| PubMed ID | 22207728 | Mgi Jnum | J:195960 |
| Mgi Id | MGI:5486275 | Doi | 10.1161/ATVBAHA.111.243675 |
| Citation | Qian F, et al. (2012) Role for the guanine nucleotide exchange factor phosphatidylinositol-3,4,5-trisphosphate-dependent rac exchanger 1 in platelet secretion and aggregation. Arterioscler Thromb Vasc Biol 32(3):768-77 |
| abstractText | OBJECTIVE: 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. |
