Thrombin induces activation of p38 MAP kinase in human platelets.
In human platelets a proline-directed kinase distinct from the ERK MAP kinases is stimulated by both thrombin and the thrombin receptor agonist peptide SFLLRN and may be involved in the activation of Ca(2+)-dependent cytosolic phospholipase A2 (Kramer, R. M., Roberts, E. F., Hyslop, P. A., Utterback, B. G., Hui, K. Y., and Jakubowski, J.A. (1995) J. Biol. Chem. 270, 14816-14823). Here we show that this kinase is identical with or closely related to p38 (the mammalian homolog of HOG1 from yeast), a recently discovered protein kinase typically activated by inflammatory cytokines and environmental stress. Further, we demonstrate that activation of this kinase by thrombin is transient (with maximal stimulation at 1 min), is accompanied by tyrosine phosphorylation, and precedes the activation of the ERK kinases. This is the first report to show that p38 kinase is activated by thrombin and to suggest a role for this MAP kinase in the thrombin-mediated signaling events during platelet activation.
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000097:blood* / Q000187:drug effects / Q000302:isolation & purification; D002852:Chromatography, Ion Exchange; D006801:Humans; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D015539:Platelet Activation; D018179:Receptors, Thrombin / Q000502:physiology; D015398:Signal Transduction; D013379:Substrate Specificity; D013917:Thrombin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D010446:Peptide Fragments; D010455:Peptides; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D019000:Phosphotyrosine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin