ADRENOCORTlCOTROPIN (ACTH) INDUCES MAP KINASE PHOSPHATASE (MKP)-1 EXPRESSION IN YI MOUSE ADRENOCORTICAL TUMOR CELLS

GOROSTIZAGA. ALEJANDRA B.; BEY, PAULA; MALOBERTI. PAULA M; PODEROSO, CECILIA; GARRIDO, MARIA R.: CORNEJO MACIEL, MARÍA F.; PODESTÁ ERNESTO J. AND PAZ. CRISTINA DEL V.

Villa Carlos paz, Cordoba

Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2002

SAIB

Adrenocorticotropin (ACTH) signaling pathway includes protein phosphorylation processes and also serine/threonine and tyrosine dephosphorylation events mediated by hormone-dependent phosphatases. MAP kinase phosphatase-1 (MKP-1) is a dual activity protein pbosphatase specifically involved in the inactivation of mitogen activated protein (MAP) kinases. Here we describe the effect of ACTH on MKP-1 mRNA and protein levels evaluated by Northem and Westem blot respectively in serum-starved Y 1 mouse adrenocortical tumor cells. ACTH increased MKP-1 mRNA levels in a time- and dose-dependent fashion. The increase was maximal (6-fold) at 1 h of stimulation and it was blunted by Actinomycin D. MKP-1 protein levels were also increased by ACTH (6-fold at 2 h of stimulation). A similar effect on MKP-1 mRNA levels was produced by 8Br-cAMP (4-fold at 1 h of stimulation). PKA inhibition by H-89 abolished the effect of 8Br-cAMP whereas it only partially reduced the effect of ACTH, suggesting that PKA-independent mechanisms would contribute to the hormonal effect. Nevertheless PKA activation still seems essential for MKP-1 induction since raises in intracellular Ca2+ and PKC activation were per se ineffective but potentiated ACTH and 8Br-cAMP action. In summary, we report here the identification of MK.P-1 as one of the phosphatases involved in the mechanism of action of ACTH.