SPATIO-TEMPORAL REGULATION OF ERK ACTIVITY BY hCG IN LEYDIG CELLS: PARTICIPATION OF DIFFERENT MAP KINASE PHOSPHATASES (MKPs).

M. MORI SEQUEIROS GARCÍA, ; N.V. GÓMEZ ; A. GOROSTIZAGA ; L. BRION; A. ACQUIER; A. DUARTE; ; C.F. MÉNDEZ ; E.J. PODESTÁ; C. PAZ.

League City

Conferencia; Conference on the Adrenal Cortex and Keith Parker Memorial Lecture; 2012

Alexander Brownie and Bernard Schimmer

Several MKP family members regulate ERK activity. We have demonstrated that nuclear MKP-1 is rapidly induced by hCG and cAMP through transcriptional and posttranslational mechanisms in MA-10 Leydig cells. MKP-1 down-regulation by siRNA increases the hormonal effects on ERK1/2 activity, StAR gene expression and steroidogenesis. Our recent studies indicate that MKP-3, a cytosolic enzyme induced by proliferative signals, is also induced by hCG. We demonstrate that hCG and 8Br-cAMP transiently increased MKP-3 mRNA levels (2-fold at 3 h stimulation). Both stimuli also increased flag-MKP-3 levels as assessed by Western blot using an anti-Flag antibody. Since the chimera is under the control of a constitutive promoter this result suggests that a hormone-induced post translational modification increases MKP-3 half-life. Moreover, 8Br-cAMP stimulation resulted in flag-MKP-3 accumulation in the cytosol and reduced ERK1/2 phosphorylation. Thus, induction of MKP-3 and MKP-1 by LH/hCG could exert a strict spatio-temporal control on MAP kinases to regulate different events such as proliferation and steroidogenesis.