Integrin-independent Tyrosine Phosphorylation of p125fak in Human Platelets Stimulated by Collagen

• Published in: The Journal of biological chemistry Vol. 276; no. 5; pp. 3167 - 3174
• Main Authors: Achison, Marcus, Elton, Catherine M., Hargreaves, Philip G., Knight, C. Graham, Barnes, Michael J., Farndale, Richard W.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 02.02.2001; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M007186200

Collagen fibers or a glycoprotein VI-specific collagen-related peptide (CRP-XL) stimulated tyrosine phosphorylation of the focal adhesion kinase, p125fak (FAK), in human platelets. An integrin α2β1-specific triple-helical peptide ligand, containing the sequence GFOGER (single-letter nomenclature, O = Hyp) was without effect. Antibodies to the α2 and β1 integrin subunits did not inhibit platelet FAK tyrosine phosphorylation caused by either collagen fibers or CRP-XL. Tyrosine phosphorylation of FAK caused by CRP-XL or thrombin, but not that caused by collagen fibers, was partially inhibited by GR144053F, an antagonist of integrin αIIbβ3. The intracellular Ca2+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 α2β1 is neither sufficient nor necessary for activation of FAK, 2) the fibrinogen receptor αIIbβ3 is not required for activation of FAK by collagen fibers, and 3) both intracellular Ca2+ and protein kinase C activity are essential intermediaries of FAK activation.