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PMID: 11238375 Published · ppublish English Journal Article

Regulation of gene expression by the small GTPase Rho through the ERK6 (p38 gamma) MAP kinase pathway.

Genes & development ·Vol. 15 ·No. 5 ·2001-03-01 ·Pages 535-53

Marinissen MJ, Chiariello M, Gutkind JS

Abstract

Small GTP-binding proteins of the Rho-family, Rho, Rac, and Cdc42, have been traditionally linked to the regulation of the cellular actin-based cytoskeleton. Rac and Cdc42 can also control the activity of JNK, thus acting in a molecular pathway transmitting extracellular signals to the nucleus. Interestingly, Rho can also regulate gene expression, albeit by a not fully understood mechanism. Here, we found that activated RhoA can stimulate c-jun expression and the activity of the c-jun promoter. As the complexity of the signaling pathways controlling the expression of c-jun has begun to be unraveled, this finding provided a unique opportunity to elucidate the biochemical routes whereby RhoA regulates nuclear events. We found that RhoA can initiate a linear kinase cascade leading to the activation of ERK6 (p38 gamma), a recently identified member of the p38 family of MAPKs. Furthermore, we present evidence that RhoA, PKN, MKK3/MKK6, and ERK6 (p38 gamma) are components of a novel signal transduction pathway involved in the regulation of gene expression and cellular transformation.

MeSH Terms
3T3 Cells Activating Transcription Factor 2 Animals Blotting, Northern Blotting, Western Calcium-Calmodulin-Dependent Protein Kinases/genetics,metabolism Cell Transformation, Neoplastic/genetics Cyclic AMP Response Element-Binding Protein/genetics,metabolism DNA-Binding Proteins/genetics,metabolism MAP Kinase Kinase 3 MAP Kinase Kinase 6 MAP Kinase Signaling System MEF2 Transcription Factors Mice Mitogen-Activated Protein Kinase 12 Mitogen-Activated Protein Kinase Kinases/genetics,metabolism Mitogen-Activated Protein Kinases/genetics,metabolism Mutation Myogenic Regulatory Factors Phosphorylation Promoter Regions, Genetic Protein Serine-Threonine Kinases/genetics,metabolism Protein-Tyrosine Kinases/genetics,metabolism Proto-Oncogene Proteins c-jun/genetics,metabolism Transcription Factor AP-1/genetics,metabolism Transcription Factors/genetics,metabolism Transcriptional Activation rhoA GTP-Binding Protein/genetics,metabolism
Chemicals
Activating Transcription Factor 2 Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins MEF2 Transcription Factors Myogenic Regulatory Factors Proto-Oncogene Proteins c-jun Transcription Factor AP-1 Transcription Factors Mitogen-Activated Protein Kinase 12 Protein-Tyrosine Kinases Protein Serine-Threonine Kinases Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinases MAP Kinase Kinase 3 MAP Kinase Kinase 6 Map2k3 protein, mouse Map2k6 protein, mouse Mitogen-Activated Protein Kinase Kinases rhoA GTP-Binding Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Marinissen M J
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Chiariello M
Gutkind J S
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.855801
Published
2001-03-01
Pages
535-53
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312639
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.855801 PMC Full Text View journal details
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