| First Author | Ramakrishnan V | Year | 1999 |
| Journal | Proc Natl Acad Sci U S A | Volume | 96 |
| Issue | 23 | Pages | 13336-41 |
| PubMed ID | 10557321 | Mgi Jnum | J:58516 |
| Mgi Id | MGI:1347746 | Doi | 10.1073/pnas.96.23.13336 |
| Citation | Ramakrishnan V, et al. (1999) Increased thrombin responsiveness in platelets from mice lacking glycoprotein V. Proc Natl Acad Sci U S A 96(23):13336-41 |
| abstractText | A role for glycoprotein (GP)V in platelet function has been proposed on the basis of observations that GP V is the major thrombin substrate on intact platelets cleaved during thrombin-induced platelet aggregation, and that GP V promotes GP Ib-IX surface expression in heterologous cells. We tested the hypotheses that GP V is involved in thrombin-induced platelet activation, in GP Ib-IX expression, and in other platelet responses by generating GP V null mice. Contrary to expectations, GP V -/- platelets were normal in size and expressed normal amounts of GP Ib-IX that was functional in von Willebrand factor binding, explaining why defects in GP V have not been observed in Bernard-Soulier syndrome, a bleeding disorder caused by a lack of functional GP Ib-IX-V. Moreover, in vitro analysis demonstrated that GP V -/- platelets were hyperresponsive to thrombin, resulting in increased fibrinogen binding and an increased aggregation response. Consistent with these findings, GP V -/- mice had a shorter bleeding time. These data support a role for GP V as a negative modulator of platelet activation. Furthermore, they suggest a new mechanism by which thrombin enhances platelet responsiveness independent of activation of the classical G-protein-coupled thrombin receptors. |
