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Lyn and PECAM-1 function as interdependent inhibitors of platelet aggregation

By Zhangyin Ming, Yu Hu, Jizhou Xiang, Peter Polewski, Peter J. Newman and Debra K. Newman

Abstract

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

Topics: Platelets and Thrombopoiesis
Publisher: American Society of Hematology
OAI identifier: oai:pubmedcentral.nih.gov:3083302
Provided by: PubMed Central
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