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PMID: 11046144 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ras-dependent regulation of c-Jun phosphorylation is mediated by the Ral guanine nucleotide exchange factor-Ral pathway.

Molecular and cellular biology ·Vol. 20 ·No. 22 ·2000-11-00 ·Pages 8480-8

de Ruiter ND, Wolthuis RM, van Dam H, Burgering BM, Bos JL

Abstract

The transcription factor c-Jun is critically involved in the regulation of proliferation and differentiation as well as cellular transformation induced by oncogenic Ras. The signal transduction pathways that couple Ras activation to c-Jun phosphorylation are still partially elusive. Here we show that an activated version of the Ras effector Rlf, a guanine nucleotide exchange factor (GEF) of the small GTPase Ral, can induce the phosphorylation of serines 63 and 73 of c-Jun. In addition, we show that growth factor-induced, Ras-mediated phosphorylation of c-Jun is abolished by inhibitory mutants of the RalGEF-Ral pathway. These results suggest that the RalGEF-Ral pathway plays a major role in Ras-dependent c-Jun phosphorylation. Ral-dependent regulation of c-Jun phosphorylation includes JNK, a still elusive JNKK, and possibly Src.

MeSH Terms
Animals Cell Differentiation/drug effects Cell Division/drug effects Cell Line/drug effects Enzyme Activation Guanine Nucleotide Exchange Factors Humans Insulin/metabolism,pharmacology JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 Mice Mitogen-Activated Protein Kinase Kinases/metabolism Mitogen-Activated Protein Kinases/metabolism Mutation Phosphorylation Pyrazoles/pharmacology Pyrimidines/pharmacology Serine Signal Transduction Transcription Factors/genetics,metabolism ral GTP-Binding Proteins/metabolism ral Guanine Nucleotide Exchange Factor/metabolism ras Proteins/metabolism src-Family Kinases/antagonists & inhibitors,metabolism
Chemicals
4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine Guanine Nucleotide Exchange Factors Insulin Pyrazoles Pyrimidines RLF protein, human Rgl2 protein, mouse Transcription Factors ral Guanine Nucleotide Exchange Factor Serine src-Family Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 Mitogen-Activated Protein Kinase Kinases ral GTP-Binding Proteins ras Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
de Ruiter N D
Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Wolthuis R M
van Dam H
Burgering B M
Bos J L
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.22.8480-8488.2000
Published
2000-11-00
Pages
8480-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC102154
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.20.22.8480-8488.2000 PMC Full Text View journal details
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