Phosphatidylinositol 3'-kinase and tyrosine-phosphatase activation positively modulate Convulxin-induced platelet activation. Comparison with collagen.
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 PLCgamma2, but blocked collagen-induced platelet aggregation as well as tyrosine phosphorylation of PLCgamma2. In contrast, Cvx-induced PLCgamma2 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 PLCgamma2 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 gamma chain signal to result in full activation and tyrosine phosphorylation of PLCgamma2 in Cvx-stimulated platelets.
Lagrue
A H
AH
Laboratoire de Recherche sur l'Hémostase et la Thrombose, Faculté Xavier Bichat, Paris, France.
Francischetti
I M
IM
Guimarães
J A
JA
Jandrot-Perrus
M
M
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D003435:Crotalid Venoms / Q000378:metabolism* / Q000494:pharmacology; D017839:Crotalus; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D037181:Lectins, C-Type; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D001152:Arsenicals; D002118:Calcium; D003094:Collagen; D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D037181:Lectins, C-Type; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010975:Platelet Aggregation Inhibitors; D017027:Protein Tyrosine Phosphatases; D014443:Tyrosine; C029341:oxophenylarsine; C028890:convulxin