Cell condition-dependent regulation of ERK5 by cAMP.
ERK5 activity is increased by agents known to activate receptor tyrosine kinases, G-protein coupled receptors, and stress response pathways. We now find a role for cAMP in the regulation of ERK5. ERK5 is activated by forskolin, isoproterenol, and epinephrine in NIH3T3 cells and C2C12 myoblasts. ERK1/2 are also activated by cAMP in NIH3T3 cells, but not in C2C12 myoblasts, demonstrating differential regulation of ERK5 and ERK1/2 by cAMP. We examined the effect of cell context on activation of ERK5 and discovered ERK5 activity is inhibited, rather than activated, by cAMP in confluent, serum-deprived NIH3T3 cells and C2C12 myoblasts. Our results suggest that regulation of MAP kinase pathways by cAMP is not only dictated by cell type, but also by cell context.
Pearson
Gray W
GW
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75390-9041, USA.
Cobb
Melanie H
MH
D016475:3T3 Cells; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D005576:Colforsin; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases