Integrin-dependent protein dephosphorylation on tyrosine induced by activation of the thrombin receptor in human platelets.
Activation of human platelets by thrombin or a thrombin receptor-activating peptide (TRAP) resulted in a decrease in tyrosine phosphorylation of two proteins, P38 and P140. Preincubation of platelets with the tyrosine phosphatase inhibitor orthovanadate prevented the tyrosine dephosphorylation of P38 and P140, and reduced platelet aggregation induced by thrombin receptor activation. When platelets were stimulated under conditions that precluded the activation of glycoprotein IIb/IIIa (dissociation of the complex by EGTA at 37 degrees C) or the binding of fibrinogen (preincubation of platelets with RGDS), tyrosine dephosphorylation of P38 and P140 was not observed. The results indicate that protein tyrosine phosphatase stimulation (a) occurs during platelet activation induced by a physiological stimulus, (b) is a positive regulatory signal for platelet aggregation and (c) is dependent on the activation of the integrin alpha IIb beta 3.
Luber
K
K
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten b.d. Universität München, Germany.
Siess
W
W
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018179:Receptors, Thrombin / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D016023:Integrins; D010446:Peptide Fragments; D018179:Receptors, Thrombin; C076901:thrombin receptor-activating peptide (P508-530); D014638:Vanadates; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases; D013917:Thrombin