cAMP EXERTS A FINE CONTROL OF MAP KINASE PHOSPHATASE-1 LEVELS. IMPLICATIONS ON GENE TRANSCRIPTIONS

BRION L.; GOROSTIZAGA A.; SUÁREZ G.; MORI SEQUEIROS GARCÍA M.; PODEROSO C.; CORNEJO MACIEL F.; PODESTÁ EJ.; PAZ C

Mar del Plata, Buenos Aires

Congreso; XLIII Reunión Anual Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2007

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

MAP kinase phosphatase-1 (MKP-1) controls nuclear MAP kinase activity with important consequences for gene transcription. In adrenal and Leydig cells, trophic hormones trigger ERK1/2 activation, a key step in Steroidogenic Acute Regulatory (StAR) protein induction and steroidogenesis. In addition, we have reported a hormone/cAMP-dependent transcriptional increase of MKP-1 in those cells. In this study we analyzed the post translational regulation of MKP-1 and its functional role on gene transcription. Western blot analysis showed that 8Br-cAMP stimulation (0-3 h) up regulates MKP-1 in MA-10 Leydig cells transiently overexpressing the protein in a magnitude higher than that observed in mock transfected cells, an effect that was reduced by blocking ERK1/2 activation. Since proteasome inhibitors also produced MKP-1 accumulation, our study suggests that PKA/ERK1/2?mediated phosphorylation of the enzyme impairs its proteasomal degradation. We also tested the role of MKP-1 on cAMP-stimulated StAR promoter activity using a reporter (luciferase) system. 8Br-cAMP stimulation (6 h) enhanced promoter activity (Control=0.36±0.03 vs 8Br=0.99±0.10, P