Phosphorylation of JAK2 in thrombin-stimulated human platelets.
We show the presence of the tyrosine kinase JAK2 in human platelets and demonstrate that it undergoes phosphorylation on tyrosine residues on challenge with the G protein receptor stimulus, thrombin, or the tyrosine phosphatase inhibitor, peroxovanadate. Thrombin-induced phosphorylation of JAK2 is inhibited by two structurally distinct inhibitors of tyrosine kinases, staurosporine and the tyrphostin ST271. The protein kinase C (PKC) inhibitor, Ro 31-8220, and intracellular Ca2+ chelator, BAPTA-AM, also inhibit thrombin-induced phosphorylation of JAK2, while the phorbol ester, phorbol dibutyrate (PDBu), and Ca2+ ionophore, A23187, induce tyrosine phosphorylation of JAK2. These results suggest that tyrosine phosphorylation of JAK2 stimulated by thrombin may be mediated downstream of phosphoinositide metabolism.
Rodríguez-Liñares
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Watson
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D000470:Alkaloids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D000001:Calcimycin / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D053614:Janus Kinase 2; D007700:Kinetics; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000097:blood*; D011518:Proto-Oncogene Proteins; D019311:Staurosporine; D013343:Styrenes / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology
D000470:Alkaloids; D002614:Chelating Agents; D007211:Indoles; D011518:Proto-Oncogene Proteins; D013343:Styrenes; C069276:peroxovanadate; C086531:ST 271; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D000001:Calcimycin; D014638:Vanadates; D004533:Egtazic Acid; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D011493:Protein Kinase C; D013917:Thrombin; D019311:Staurosporine; C064758:Ro 31-8220