| First Author | Chrzanowska-Wodnicka M | Year | 2005 |
| Journal | J Clin Invest | Volume | 115 |
| Issue | 3 | Pages | 680-7 |
| PubMed ID | 15696195 | Mgi Jnum | J:96758 |
| Mgi Id | MGI:3531385 | Doi | 10.1172/JCI22973 |
| Citation | Chrzanowska-Wodnicka M, et al. (2005) Rap1b is required for normal platelet function and hemostasis in mice. (Correction 115: 2296). J Clin Invest 115(3):680-7 |
| abstractText | Rap1b, an abundant small GTPase in platelets, becomes rapidly activated upon stimulation with agonists. Though it has been implicated to act downstream from G protein-coupled receptors (GPCRs) and upstream of integrin alpha IIbbeta3, the precise role of Rap1b in platelet function has been elusive. Here we report the generation of a murine rap1b knockout and show that Rap1b deficiency results in a bleeding defect due to defective platelet function. Aggregation of Rap1b-null platelets is reduced in response to stimulation with both GPCR-linked and GPCR-independent agonists. Underlying the defective Rap1b-null platelet function is decreased activation of integrin alphaIIbbeta3 in response to stimulation with agonists and signaling downstream from the integrin alpha IIbbeta3. In vivo, Rap1b-null mice are protected from arterial thrombosis. These data provide genetic evidence that Rap1b is involved in a common pathway of integrin activation, is required for normal hemostasis in vivo, and may be a clinically relevant antithrombotic therapy target. |
