First Author | Ming Z | Year | 2011 |
Journal | Blood | Volume | 117 |
Issue | 14 | Pages | 3903-6 |
PubMed ID | 21297004 | Mgi Jnum | J:172845 |
Mgi Id | MGI:5009111 | Doi | 10.1182/blood-2010-09-304816 |
Citation | Ming Z, et al. (2011) Lyn and PECAM-1 function as interdependent inhibitors of platelet aggregation. Blood 117(14):3903-6 |
abstractText | Inhibition of platelet responsiveness is important to control pathologic thrombus formation. Platelet-endothelial cell adhesion molecule-1 (PECAM-1) and the Src family kinase Lyn inhibit platelet activation by the glycoprotein VI (GPVI) collagen receptor; however, it is not known whether PECAM-1 and Lyn function in the same or different inhibitory pathways. In these studies, we found that, relative to wild-type platelets, platelets derived from PECAM-1-deficient, Lyn-deficient, or PECAM-1/Lyn double-deficient mice were equally hyperresponsive to stimulation with a GPVI-specific agonist, indicating that PECAM-1 and Lyn participate in the same inhibitory pathway. Lyn was required for PECAM-1 tyrosine phosphorylation and subsequent binding of the Src homology 2 domain-containing phosphatase-2, SHP-2. These results support a model in which PECAM-1/SHP-2 complexes, formed in a Lyn-dependent manner, suppress GPVI signaling. |