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

• Published in: FEBS letters 1999-04, Vol.448 (1), p.95-100
• Main Authors: Lagrue, Anne-Helène, Francischetti, Ivo M.B., Guimarães, Jorge A., Jandrot-Perrus, Martine
• Format: Article
• Language: English
• Subjects: Animals; Arsenicals - pharmacology; Blood Platelets - drug effects; Blood Platelets - physiology; Calcium - metabolism; Collagen - metabolism; Collagen - pharmacology; Convulxin; Crotalid Venoms - metabolism; Crotalid Venoms - pharmacology; Crotalus; Crotalus durissus terrificus; Cvx, convulxin; Enzyme Activation; Enzyme Inhibitors - pharmacology; Inositol Phosphates - biosynthesis; Lectins, C-Type; PAO, phenylarsine oxide (PTPase inhibitor); PH domain, pleckstrin homology domain; Phenylarsine oxide; Phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phospholipase Cγ; Phosphorylation; PI3-K, phosphatidylinositol 3′-kinase; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors - pharmacology; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - metabolism; Protein tyrosine phosphorylation; PTPase, tyrosine phosphatase; PY20, antiphosphotyrosine monoclonal antibody; Tyrosine - metabolism; Tyrosine phosphatase; Wortmannin
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00340-3

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.