IMPACT OF THE POST-TRANSLATIONAL REGULATION OF MAPK PHOSPHATASE-1 (MKP-1) ON cAMPC-INDUCED NUR77 EXPRESSION

MORI SEQUEIROS GARCÍA MM; GOROSTIZAGA AB; BRION L; NUDLER S; GONZALEZ-CALVAR S; PAZ C

Chicago. Illinois

Congreso; Conference on the Adrenal Cortex 2014; 2014

In MA-10 Leydig cells, LH receptor activation up-regulates MKP-1 by transcriptional and post-translational mechanisms. We analyze 1) whether the cAMP-mediated expression of NUR77, a factor involved in the expression of several steroidogenic genes like STARD1, is an ERK-dependent process and 2) the impact of MKP-1 and its phosphorylation in ERK consensus sites on such expression. In MA-10 transfected cells, the half-life of flag-MKP-1-S296A-S323A and flag-MKP-1-S359A-S364A increased (120 min) and decreased (45 min), respectively, after cAMP stimulation, as compared with flag-MKP-1 wild type (120 min), which suggests that S359 and S364 phosphorylation stabilizes MKP-1. We demonstrate, for the first time, that the cAMP-induced increase in NUR77 promoter activity and mRNA levels are ERK-dependent processes in MA-10 Leydig cells. Accordingly, flag-MKP-1 expression reduces the effect of cAMP on NUR77 expression, while flag-MKP-1-S359A-S364A has no effects. It is concluded that multi-site ERK-mediated phosphorylation is involved in MKP-1 half-life, which in turn modulates ERK-dependent processes, like NUR77 expression.