Related Experiment Video
Updated: Oct 9, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Activation of mitogen-activated protein kinase phosphatase 2 by gonadotropin-releasing hormone
T Zhang1, J M Mulvaney, M S Roberson
1Department of Biomedical Sciences, College of Veterinary Medicine, T6-008a Veterinary Research Tower, Cornell University, Ithaca, NY 14853, USA.
Abstract:
The aim of these studies was to identify the signaling mechanism(s) that contribute to GnRH-induced expression of MAPK phosphatase (MKP)-2, a dual specificity phosphatase that selectively inactivates MAPKs. GnRH receptor activation induced MKP-2 expression in both clonal (alphaT3-1) and primary gonadotropes. Activation of PKC isozymes was sufficient and required for MKP-2 induction. Inhibition of the extracellular signal-regulated kinase (ERK) or c-Jun N-terminal kinase (JNK) but not the p38 MAPK cascade was sufficient to block GnRH-induced MKP-2 expression. Induction of MKP-2 by GnRH was dependent on elevation in intracellular Ca(2+). Inhibition of Ca(2+) influx through L-type voltage-gated calcium channels blocked GnRH-induced MKP-2 expression. Depletion of intracellular Ca(2+) stores with thapsigargin blocked MKP-2 activation by GnRH independent of ERK and JNK activity. These results support the conclusion that MKP-2 induction by GnRH occurs via MAPK-dependent and -independent pathways. One mechanism requires GnRH-induced ERK and JNK activation, while a second MAPK-independent pathway requires a thapsigargin-sensitive calcium signal.
More Related Videos
09:30Dual Somatic Recordings from Gonadotropin-Releasing Hormone (GnRH) Neurons Identified by Green Fluorescent Protein (GFP) in Hypothalamic Slices
Published on: February 23, 2010
07:14Healthy Brain-pituitary Slices for Electrophysiological Investigations of Pituitary Cells in Teleost Fish
Published on: August 16, 2018
Related Concept Videos
Secondary Messengers in Hormone Action
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
Amplifying Signals via Enzymatic Cascade
MAPK Signaling Cascades
GPCRs Regulate Adenylyl Cylase Activity
Two...
cAMP-dependent Protein Kinase Pathways
Mitogens and the Cell Cycle