Thrombin Induces Activation of p38 MAP Kinase in Human Platelets

Ruth M Kramer,Edda F Roberts,Beth A Strifler,Edward M Johnstone

doi:10.1074/jbc.270.46.27395

Ruth M Kramer, Edda F Roberts + Show 2 more

Open Access

https://doi.org/10.1074/jbc.270.46.27395

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Abstract

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.

Highlights

In human platelets thrombin activates several kinases that readily phosphorylate the Thr669 peptide derived from the epidermal growth factor receptor [1]
Han et al [10] first described this novel kinase p38 Kinase Activation in Thrombin-stimulated Platelets of apparent molecular mass of 38 kDa in cells of monocytic lineage, observing that it is rapidly phosphorylated on tyrosine residues in response to endotoxin
Our studies show that the p38 kinase is present in human platelets, where it is transiently and potently stimulated by thrombin

Summary

Introduction

In human platelets thrombin activates several kinases that readily phosphorylate the Thr669 peptide derived from the epidermal growth factor receptor [1]. When extracts from control and thrombin-stimulated platelets were applied to MonoQ in buffer containing 150 mM NaCl, ERK1/2 flowed through the column.

Results

Conclusion