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PMID: 16616457 Published · ppublish English Journal Article Review

FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A.

Cellular signalling ·Vol. 18 ·No. 9 ·2006-09-00 ·Pages 1351-9

Hunzicker-Dunn M, Maizels ET

Abstract

Follicle-stimulating hormone (FSH) is necessary and sufficient to induce maturation of ovarian follicles to a mature, preovulatory phenotype in the intact animal, resulting in the generation of mature eggs and production of estrogen. FSH accomplishes these actions by inducing a complex pattern of gene expression in target granulosa cells that is regulated by input from many different signaling cascades, including those for the extracellular regulated kinases (ERKs), p38 mitogen-activated protein kinases (MAPKs), and phosphatidylinositol-3 kinase (PI3K). The upstream kinase that appears to be responsible for initiating all of the signaling that regulates gene expression in these epithelial cells is protein kinase A (PKA). PKA not only signals to directly phosphorylate transcription factors like cAMP response element binding protein and to promote chromatin remodeling by phosphorylating histone H3, this versatile kinase also enhances the activity of the p38 MAPK, ERK, and PI3K pathways. Additionally, accumulating evidence suggests that activation of a single signaling cascade downstream of PKA is not sufficient to activate target gene expression. Rather, cross-talk between and among signaling cascades is required. We will review the signaling cascades activated by FSH in granulosa cells and how these cascades contribute to the regulation of select target gene expression.

MeSH Terms
Animals Cyclic AMP Response Element-Binding Protein/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism Enzyme Activation Female Follicle Stimulating Hormone/metabolism Forkhead Transcription Factors/metabolism Gene Expression Regulation Granulosa Cells/physiology Histones/metabolism Phosphatidylinositol 3-Kinases/metabolism Protein Tyrosine Phosphatases/metabolism Signal Transduction/physiology Tuberous Sclerosis Complex 2 Protein Tumor Suppressor Proteins/metabolism p38 Mitogen-Activated Protein Kinases/metabolism
Chemicals
Cyclic AMP Response Element-Binding Protein Forkhead Transcription Factors Histones Tuberous Sclerosis Complex 2 Protein Tumor Suppressor Proteins Follicle Stimulating Hormone Phosphatidylinositol 3-Kinases Cyclic AMP-Dependent Protein Kinases p38 Mitogen-Activated Protein Kinases Protein Tyrosine Phosphatases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hunzicker-Dunn Mary
Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. mehd@wsu.edu
Maizels Evelyn T
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Article Info
Journal
Cellular signalling
Abbr.
Cell Signal
ISSN
0898-6568
DOI
10.1016/j.cellsig.2006.02.011
Email
mehd@wsu.edu
Published
2006-09-00
Epub
2006-00-17
Pages
1351-9
Language
English
Region
England
NLM ID
8904683
PMCID
PMC1564187
Subset
IM
Grants
NICHD NIH HHS · P01 HD021921 · United States
External Links
PubMed source DOI: 10.1016/j.cellsig.2006.02.011 PMC Full Text View journal details
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