Lyn and PECAM-1 function as interdependent inhibitors of platelet aggregation. Blood 2011 Apr 07;117(14):3903-6
Date
02/08/2011Pubmed ID
21297004Pubmed Central ID
PMC3083302DOI
10.1182/blood-2010-09-304816Scopus ID
2-s2.0-79953835599 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
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.
Author List
Ming Z, Hu Y, Xiang J, Polewski P, Newman PJ, Newman DKAuthors
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinPeter J. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCells, Cultured
Drug Synergism
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Multiprotein Complexes
Platelet Aggregation
Platelet Aggregation Inhibitors
Platelet Endothelial Cell Adhesion Molecule-1
Platelet Membrane Glycoproteins
Protein Tyrosine Phosphatase, Non-Receptor Type 11
src-Family Kinases
