Integrin-independent Tyrosine Phosphorylation of p125fakin Human Platelets Stimulated by Collagen

Marcus Achison, Catherine M. Elton, Philip G. Hargreaves, C. Graham Knight, Michael J. Barnes, Richard W. Farndale
2000 Journal of Biological Chemistry  
Collagen fibers or a glycoprotein VI-specific collagenrelated peptide (CRP-XL) stimulated tyrosine phosphorylation of the focal adhesion kinase, p125 fak (FAK), in human platelets. An integrin ␣ 2 ␤ 1 -specific triple-helical peptide ligand, containing the sequence GFOGER (single-letter nomenclature, O ‫؍‬ Hyp) was without effect. Antibodies to the ␣ 2 and ␤ 1 integrin subunits did not inhibit platelet FAK tyrosine phosphorylation caused by either collagen fibers or CRP-XL. Tyrosine
more » ... ion of FAK caused by CRP-XL or thrombin, but not that caused by collagen fibers, was partially inhibited by GR144053F, an antagonist of integrin ␣ IIb ␤ 3 . The intracellular Ca 2؉ chelator, BAPTA, and the protein kinase C inhibitor, Ro31-8220, were each highly effective inhibitors of the FAK tyrosine phosphorylation caused by collagen or CRP-XL. These data suggest that, in human platelets, 1) occupation or clustering of the integrin ␣ 2 ␤ 1 is neither sufficient nor necessary for activation of FAK, 2) the fibrinogen receptor ␣ IIb ␤ 3 is not required for activation of FAK by collagen fibers, and 3) both intracellular Ca 2؉ and protein kinase C activity are essential intermediaries of FAK activation.
doi:10.1074/jbc.m007186200 pmid:11110790 fatcat:6jrwqrvfb5hvnkxcj2mrgokpiu