Cyclic AMP-elevating agents induce the expression of MAP kinase phosphatase-1 in PC12 cells

Stimulation of pheochromocytoma PC12 cells by cAMP-elevating agents caused the induction of the immediate early gene 3CH134, which encodes MAP kinase phosphatase-1 (MKP-1). Forskolin was as potent as serum in stimulating MKP- 1 gene expression, whereas dibutyryl-cAMP and neuropeptide PACAP were less effective, Induction of the MKP-1 gene was accompanied by neo-synthesis of MKP-1 protein. MAP kinase activation was not involved in the caMP-induced M KP-1 gene expression, The MAP kinase inactivation, that would result from M KP-1 induction in response to increased intracellular cAMP level, contribut es to explain how hormones or neurotransmitters signaling through cAMP infl uence cell growth and differentiation. (C) 2000 Federation of European Bioc hemical Societies. Published by Elsevier Science B.V. All rights reserved.