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Phosphatidylinositol 3′‐kinase and tyrosine‐phosphatase activation positively modulate Convulxin‐induced platelet activation. Comparison with collagen
Author(s) -
Lagrue Anne-Helène,
Francischetti Ivo M.B.,
Guimarães Jorge A.,
Jandrot-Perrus Martine
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00340-3
Subject(s) - wortmannin , tyrosine phosphorylation , gpvi , protein tyrosine phosphatase , phosphorylation , platelet activation , chemistry , phosphatidylinositol , tyrosine , platelet , microbiology and biotechnology , phosphatase , biochemistry , phenylarsine oxide , syk , tyrosine kinase , signal transduction , receptor , platelet membrane glycoprotein , biology , immunology
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 [Ca 2+ ] 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.