p38 mitogen-activated protein kinase phosphorylates cytosolic phospholipase A2 (cPLA2) in thrombin-stimulated platelets. Evidence that proline-directed phosphorylation is not required for mobilization of arachidonic acid by cPLA2
| Autor: | R M, Kramer, E F, Roberts, S L, Um, A G, Börsch-Haubold, S P, Watson, M J, Fisher, J A, Jakubowski |
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| Rok vydání: | 1996 |
| Předmět: |
Blood Platelets
Mitogen-Activated Protein Kinase 1 Arachidonic Acid Mitogen-Activated Protein Kinase 3 Proline Thrombin In Vitro Techniques Platelet Activation p38 Mitogen-Activated Protein Kinases Peptide Fragments Phospholipases A Kinetics Phospholipases A2 Cytosol Calcium-Calmodulin-Dependent Protein Kinases Humans Calcium Receptors Thrombin Enzyme Inhibitors Mitogen-Activated Protein Kinases Phosphorylation |
| Zdroj: | The Journal of biological chemistry. 271(44) |
| ISSN: | 0021-9258 |
| Popis: | The Ca2+-sensitive 85-kDa cytosolic phospholipase A2 (cPLA2) is responsible for thrombin-stimulated mobilization of arachidonic acid for the synthesis of thromboxane A2 in human platelets. We have previously shown that thrombin activates p38 kinase, a recently discovered new member of the mitogen-activated protein kinase family (Kramer, R. M., Roberts, E. F., Strifler, B. A., and Johnstone, E. M. (1995) J. Biol. Chem. 270, 27395-27398) and also induces phosphorylation of cPLA2, thereby increasing its intrinsic catalytic activity. In the present study we have examined the role of p38 kinase in the phosphorylation and activation of cPLA2 in stimulated platelets. We have observed that activation of p38 kinase accompanies receptor-mediated events in platelets and coincides with cPLA2 phosphorylation. Furthermore, in the presence of inhibitors of p38 kinase, the proline-directed phosphorylation of cPLA2 was completely blocked in platelets stimulated with the thrombin receptor agonist peptide SFLLRN and was suppressed during the early (up to 2 min) phase of platelet stimulation caused by thrombin. Unexpectedly, we found that prevention of proline-directed phosphorylation of cPLA2 in stimulated platelets did not attenuate its ability to release arachidonic acid from platelet phospholipids. We conclude that: 1) cPLA2 is a physiological target of p38 kinase; 2) p38 kinase is involved in the early phosphorylation of cPLA2 in stimulated platelets; and 3) proline-directed phosphorylation of cPLA2 is not required for its receptor-mediated activation. |
| Databáze: | OpenAIRE |
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