Phosphatidylinositol 3'-kinase and tyrosine-phosphatase activation positively modulate Convulxin-induced platelet activation. Comparison with collagen

Anne Helène Lagrue, Ivo M.B. Francischetti, Jorge A. Guimarães, Martine Jandrot-Perrus

Research output: Contribution to journalArticlepeer-review

Abstract

In this report we have studied the role of phosphatidylinositol 3'-kinase (PI3-K) and tyrosine phosphatase activation on platelet activation by Convulxin (Cvx). Wortmannin, a specific PI3-K inhibitor, and phenylarsine oxide (PAO), a sulfhydryl reagent that inhibits tyrosine phosphatase (PTPase), block Cvx-induced platelet aggregation, granule secretion, inositol phosphate production, and increase in [Ca2+](i). However, PAO does not inhibit Cvx-induced tyrosine phosphorylation of platelet proteins, including Syk and PLCγ2, but blocked collagen-induced platelet aggregation as well as tyrosine phosphorylation of PLCγ2. In contrast, Cvx-induced PLCγ2 tyrosyl phosphorylation was partially inhibited by wortmannin. We conclude that (i) although Cvx and collagen activate platelets by a similar mechanism, different regulatory processes are specific to each agonist; (ii) mechanisms other than tyrosine phosphorylation regulate PLCγ2 activity; and (iii) besides protein tyrosine kinases, PI3-K (and PTPase) positively modulate platelet activation by both Cvx and collagen, and this enzyme is required for effective transmission of GPVI-Fc receptor γ chain signal to result in full activation and tyrosine phosphorylation of PLCγ2 in Cvx-stimulated platelets. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalFEBS Letters
Volume448
Issue number1
DOIs
StatePublished - Apr 2 1999
Externally publishedYes

Keywords

  • Convulxin
  • Crotalus durissus terrificus
  • Phenylarsine oxide
  • Phosphatidylinositol 3-kinase
  • Phospholipase Cγ
  • Protein tyrosine phosphorylation
  • Tyrosine phosphatase
  • Wortmannin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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