MAP KINASE PHOPHATASE-1 GENE EXPRESIÓN INDUCED BY 8BR-cAMP IS INDEPENDENT OF ERK1/2 ACTIVATION

A. GOROSTIZAGA, L. BRION, F. CORNEJO MACIEL, E.J. PODESTÁ, C. PAZ

Pinamar, Buenos Aires, Argentina

Congreso; XLI Reunión Anual Sociedad Argentina de Investigación Bioquímica y Biología Molecular.; 2005

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

MAP kinase phosphatase-1 (MKP-1) is a dual activity phosphatase involved in the inactivation of MAP kinases (MAKPs). Several stimuli that activate MAKPs also trigger MKP-1 gene induction. We have already demonstrated that cAMP promotes MKP-1 induction in MA-10 Leydig cells. Since it is known that cAMP also promotes ERK1/2 activation in these cells, we aimed to determine if MAPKs mediate MKP-1 induction triggered by cAMP. For this purpose we studied the effect of the ERK1/2 inhibitor PD98059 on MKP-1 mRNA levels in MA-10 cells. Northern blot analysis revealed a notable increase of MKP-1 mRNA levels in cells exposed to 8Br-cAMP (1 h). This effect was not overcome by PD98059, even when this compound was effective to abrogate the ERK1/2 activation promoted by the analogue of the cyclic nucleotide. In addition, we determined that the effects of 8Br-cAMP on MKP-1 and ERK1/2 were both blunted by a PKA inhibitor, H89. Taken together, all these data suggest that in MA-10 cells the PKA activation prompts MKP-1 gene expression by an ERK1/2- independent mechanism. Supported by CONICET, ANPCyT and UBA.