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PMID: 11909979 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts.

Molecular and cellular biology ·Vol. 22 ·No. 8 ·2002-04-00 ·Pages 2871-81

Wiggin GR, Soloaga A, Foster JM, Murray-Tait V, Cohen P, Arthur JS

Abstract

Using mouse knockouts for mitogen- and stress-activated protein kinase 1 (MSK1) and MSK2 and a double knockout of both MSK1 and MSK2, we show that these protein kinases are required for the stress-induced phosphorylation of transcription factors CREB and ATF1 in primary embryonic fibroblasts. In contrast mitogen-induced phosphorylation of CREB and ATF1 is greatly reduced but not totally abolished. The mitogen- and stress-induced phosphorylation of CREB at Ser133 has been linked to the transcription of several immediate early genes, including c-fos, junB, and egr1. The knockout of both MSK1 and MSK2 resulted in a 50% reduction in c-fos and junB gene transcription in response to anisomycin or UV-C radiation but only a small reduction in response to tetradecanoyl phorbol acetate or epidermal growth factor in fibroblasts. The transcription of egr1 in response to both mitogenic and stress stimuli, as well as stress-induced apoptosis, was unaffected in the MSK1/MSK2 double knockout.

MeSH Terms
Activating Transcription Factor 1 Animals Apoptosis Calcium-Calmodulin-Dependent Protein Kinases/deficiency,genetics,physiology Cell Division Cells, Cultured Cyclic AMP Response Element-Binding Protein/metabolism DNA-Binding Proteins Enzyme Activation Fibroblasts/metabolism Genes, Immediate-Early Mice Mice, Knockout Mitogen-Activated Protein Kinases/metabolism Phosphorylation Protein Serine-Threonine Kinases/deficiency,genetics,physiology Ribosomal Protein S6 Kinases, 90-kDa Transcription Factors/metabolism Transcription, Genetic p38 Mitogen-Activated Protein Kinases
Chemicals
Activating Transcription Factor 1 Atf1 protein, mouse Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins Transcription Factors Protein Serine-Threonine Kinases Ribosomal Protein S6 Kinases, 90-kDa Rps6ka4 protein, mouse mitogen and stress-activated protein kinase 1 Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wiggin Giselle R
MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
Soloaga Ana
Foster Julia M
Murray-Tait Victoria
Cohen Philip
Arthur J Simon C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.22.8.2871-2881.2002
Published
2002-04-00
Pages
2871-81
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC133730
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.22.8.2871-2881.2002 PMC Full Text View journal details
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