Impact of the Post-Translational Regulation of MAPK Phosphatase-1 (MKP-1) on cAMP-Induced NUR77 Expression

M. MORI SEQUEIROS GARCÍA; A. GOROSTIZAGA; L. BRION; S. NUDLER; S. GONZALEZ-CALVAR; C. PAZ

Chicago, Illinois

Conferencia; Adrenal 2014; 2014

Endocrine Society

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.