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

FEBS Letters

Lagrue, Anne-Helène¹  Francischetti, Ivo M.B.¹  Jandrot-Perrus, Martine¹  Guimarães, Jorge A.² 

[1] Laboratoire de Recherche sur l'Hémostase et la Thrombose, Faculté Xavier Bichat, P.O. Box 416, 75870 Paris Cedex 18, France;Department of Medical Biochemistry, ICB/CCS, Federal University of Rio de Janeiro, Cidade Universitária, Ilha do Fundáo, C.P. 68041, CEP 21941-590, Rio de Janeiro, Brazil

关键词: Convulxin;    Phospholipase Cγ;    Protein tyrosine phosphorylation;    Phenylarsine oxide;    Phosphatidylinositol 3-kinase;    Tyrosine phosphatase;    Wortmannin;    Crotalus durissus terrificus;    Cvx;    convulxin;    PAO;    phenylarsine oxide (PTPase inhibitor);    PH domain;    pleckstrin homology domain;    PI3-K;    phosphatidylinositol 3′-kinase;    PTPase;    tyrosine phosphatase;    PY20;    antiphosphotyrosine monoclonal antibody;   

DOI  :  10.1016/S0014-5793(99)00340-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown