Differential regulation of parallel mitogen-activated protein kinases in cardiac myocytes revealed by phosphatase inhibition.
Previous studies have suggested that the contribution of inducible phosphatases to ERK MAPK deactivation is both cell-type- and agonist-specific. The aim of this study was to define the role of inducible phosphatases in ERK MAPK regulation in cardiac myocytes. We examined the kinetics of activation/deactivation of ERK MAPKs following the exposure of cardiac myocytes to endothelin-1 or phorbol ester. Deactivation was prevented by inhibition of protein synthesis indicating a contribution of inducible phosphatases. In contrast, okadaic acid failed to prolong ERK MAPK activation, but activated three myelin basic protein kinases (MBPKs, 55, 62, and 87 kDa) and two c-Jun kinases (46 and 55 kDa). Although the identity of the MBPKs is unknown, the c-Jun kinases corresponded to JNK MAPKs. Simultaneous exposure of cardiac myocytes to okadaic acid and osmotic shock potentiated JNK MAPK activation. Thus, inducible phosphatases regulate ERK MAPK deactivation, whereas okadaic acid-sensitive phosphatases regulate JNK MAPKs and three novel MBPKs.
Andersson
M B
MB
William Harvey Research Institute, Charterhouse Square, London, EC1M 6BQ, England.
Ketterman
A J
AJ
Bogoyevitch
M A
MA
D000818:Animals; D000831:Animals, Newborn; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3; D048031:JNK Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009206:Myocardium / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats
D019332:Endothelin-1; D010703:Phorbol Esters; D011500:Protein Synthesis Inhibitors; D019319:Okadaic Acid; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D010744:Phosphoric Monoester Hydrolases