TY - JOUR
T1 - Phosphatidylinositol 3'-kinase and tyrosine-phosphatase activation positively modulate Convulxin-induced platelet activation. Comparison with collagen
AU - Lagrue, Anne Helène
AU - Francischetti, Ivo M.B.
AU - Guimarães, Jorge A.
AU - Jandrot-Perrus, Martine
N1 - Funding Information:
This work was supported in part by grants from the European Community (CI1*CT940073) and University Paris 7. The authors acknowledge Brenda Rae Marshall for the preparation of the manuscript.
PY - 1999/4/2
Y1 - 1999/4/2
N2 - 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.
AB - 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.
KW - Convulxin
KW - Crotalus durissus terrificus
KW - Phenylarsine oxide
KW - Phosphatidylinositol 3-kinase
KW - Phospholipase Cγ
KW - Protein tyrosine phosphorylation
KW - Tyrosine phosphatase
KW - Wortmannin
UR - http://www.scopus.com/inward/record.url?scp=0033033956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033033956&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(99)00340-3
DO - 10.1016/S0014-5793(99)00340-3
M3 - Article
C2 - 10217417
AN - SCOPUS:0033033956
SN - 0014-5793
VL - 448
SP - 95
EP - 100
JO - FEBS Letters
JF - FEBS Letters
IS - 1
ER -