Regulation of tyrosine phosphorylation by integrins

J. S. Brugge, E. A. Clark, W. King, C. Miranti, X. M. Zhou, S. S. Shatti

Research output: Contribution to journalArticlepeer-review


We have previously shown that fibrinogen binding to its integrin receptor, αIIbβ3, is required for thrombin-induced tyrosine phosphorylation of multiple piatelet proteins. The platelet system has been valuable in dissecting the intracellular signaling events that transduce integrin-regulated changes in cell behavior. We have found that αIIbβ3 regulated tyrosine phosphorylation could be separated into two distinct events: 1) the phosphorylation of p 140 and several proteins of Mr 50-72 Kd (p50-72), which is induced by dimerization of integrin receptors with fibrinogen, and 2) the phosphorylation of p95/97 and the protein tyrosine kinase, p125FAK, which is dependent on fibrinogen-induced platelet aggregation and a second costimulatory event that requires protein kinase C and calcium. The induction of tyrosine phosphorylation of all of these proteins was inhibited in cytochalasin D treated platelets, suggesting that actin-dependent cytoskeletal complexes may couple the integrins with tyrosine kinases and their substrates. At least three classes of tyrosine protein kinases appear to participate in these events: p125FAK,which is activated following platelet aggregation; pp60src, which is activated independent of αIIbβ3 but redistributes to integrin-regulated cytoskeletal complexes after platelet aggregation, and Syk, which is phosphorylated on tyrosine following dimerization of αIIbβ3 by fibrinogen. The mechanisms involved in the activation of these kinases and the roles of these kinases In integrin mediated signal transduction will be discussed. In addition, studies In flbroblasts to dissect the signaling pathways involved in integrin activation of tyrosine phosphorylation will be presented.

Original languageEnglish (US)
Pages (from-to)A989
JournalFASEB Journal
Issue number6
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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