| First Author | Kim S | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 47 | Pages | 34230-8 |
| PubMed ID | 24106269 | Mgi Jnum | J:204983 |
| Mgi Id | MGI:5543842 | Doi | 10.1074/jbc.M113.504928 |
| Citation | Kim S, et al. (2013) RhoG protein regulates glycoprotein VI-Fc receptor gamma-chain complex-mediated platelet activation and thrombus formation. J Biol Chem 288(47):34230-8 |
| abstractText | We investigated the mechanism of activation and functional role of a hitherto uncharacterized signaling molecule, RhoG, in platelets. We demonstrate for the first time the expression and activation of RhoG in platelets. Platelet aggregation, integrin alphaIIbbeta3 activation, and alpha-granule and dense granule secretion in response to the glycoprotein VI (GPVI) agonists collagen-related peptide (CRP) and convulxin were significantly inhibited in RhoG-deficient platelets. In contrast, 2-MeSADP- and AYPGKF-induced platelet aggregation and secretion were minimally affected in RhoG-deficient platelets, indicating that the function of RhoG in platelets is GPVI-specific. CRP-induced phosphorylation of Syk, Akt, and ERK, but not SFK (Src family kinase), was significantly reduced in RhoG-deficient platelets. CRP-induced RhoG activation was consistently abolished by a pan-SFK inhibitor but not by Syk or PI3K inhibitors. Interestingly, unlike CRP, platelet aggregation and Syk phosphorylation induced by fucoidan, a CLEC-2 agonist, were unaffected in RhoG-deficient platelets. Finally, RhoG(-/-) mice had a significant delay in time to thrombotic occlusion in cremaster arterioles compared with wild-type littermates, indicating the important in vivo functional role of RhoG in platelets. Our data demonstrate that RhoG is expressed and activated in platelets, plays an important role in GPVI-Fc receptor gamma-chain complex-mediated platelet activation, and is critical for thrombus formation in vivo. |
