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J Mol Endocrinol. 2006 Feb;36(1):41-50.

Role of MAP kinase phosphatases in GnRH-dependent activation of MAP kinases.

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  • 1Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.


GnRH controls the synthesis and release of the pituitary gonadotropic hormones. MAP kinase (MAPK) cascades, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways, are crucial for GnRH-induced gene activation. In the present study, we investigated the function of GnRH-induced MAPK phosphatases (MKPs) using an in vivo mouse model as well as the alphaT3-1 cell line. Following GnRH agonist stimulation, in vivo gene profiling demonstrated that both MKP-1 and MKP-2 are induced with distinct temporal profiles, suggesting differential roles of these MKPs in the regulation of MAPK activation. Elevated activity of MKP-2 in alphaT3-1 cells, through either overexpression or activation of the endogenous MKP-2 gene, was correlated with inhibition of GnRH-induced activation of ERK and JNK, as well as the expression of ERK- and JNK-dependent proto-oncogenes. These data supported the conclusion that GnRH-induced MKPs likely serve as negative feedback regulators that modulate MAPK activity and function in the GnRH signaling pathway.

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