Journal article
Follicle-stimulating Hormone Activates Extracellular Signal-regulated Kinase but Not Extracellular Signal-regulated Kinase Kinase through a 100-kDa Phosphotyrosine Phosphatase
The Journal of biological chemistry, Vol.278(9), pp.7167-7179
02/28/2003
Handle:
https://hdl.handle.net/2376/108988
PMCID: PMC1564188
PMID: 12493768
Abstract
In this report we sought to elucidate the mechanism by which the follicle-stimulating hormone (FSH) receptor signals to promote activation of the p42/p44 extracellular signal-regulated protein kinases (ERKs) in granulosa cells. Results show that the ERK kinase MEK and upstream intermediates Raf-1, Ras, Src, and L-type Ca
2+
channels are already partially activated in vehicle-treated cells and that FSH does not further activate them. This tonic stimulatory pathway appears to be restrained at the level of ERK by a 100-kDa phosphotyrosine phosphatase that associates with ERK in vehicle-treated cells and promotes dephosphorylation of its regulatory Tyr residue, resulting in ERK inactivation. FSH promotes the phosphorylation of this phosphotyrosine phosphatase and its dissociation from ERK, relieving ERK from inhibition and resulting in its activation by the tonic stimulatory pathway and consequent translocation to the nucleus. Consistent with this premise, FSH-stimulated ERK activation is inhibited by the cell-permeable protein kinase A-specific inhibitor peptide Myr-PKI as well as by inhibitors of MEK, Src, a Ca
2+
channel blocker, and chelation of extracellular Ca
2+
. These results suggest that FSH stimulates ERK activity in immature granulosa cells by relieving an inhibition imposed by a 100-kDa phosphotyrosine phosphatase.
Metrics
11 Record Views
Details
- Title
- Follicle-stimulating Hormone Activates Extracellular Signal-regulated Kinase but Not Extracellular Signal-regulated Kinase Kinase through a 100-kDa Phosphotyrosine Phosphatase
- Creators
- Joshua Cottom - From the Departments of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611Lisa M Salvador - From the Departments of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611Evelyn T Maizels - From the Departments of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611Scott Reierstad - From the Departments of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611Youngkyu Park - From the Departments of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611Daniel W Carr - Veterans Affairs Medical Center and Oregon Health Sciences University, Portland, Oregon 97201Monika A Davare - Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706Johannes W Hell - Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706Stephen S Palmer - Serono Reproductive Biology Institute, Rockland, Massachusetts 02370Paul Dent - Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298Hisaaki Kawakatsu - Lung Biology Center, University of California, San Francisco, California 94110, andMasato Ogata - Biomedial Research Center, Osaka University Medical School, Osaka 565, JapanMary Hunzicker-Dunn - From the Departments of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611
- Publication Details
- The Journal of biological chemistry, Vol.278(9), pp.7167-7179
- Academic Unit
- Molecular Biosciences, School of
- Identifiers
- 99900547643101842
- Language
- English
- Resource Type
- Journal article