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PMID: 9878058 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1.

The EMBO journal ·Vol. 18 ·No. 1 ·1999-01-04 ·Pages 145-55

Ishimaru S, Williams R, Clark E, Hanafusa H, Gaul U

Abstract

The cellular signal transduction pathways by which C3G, a RAS family guanine nucleotide exchange factor, mediates v-crk transformation are not well understood. Here we report the identification of Drosophila C3G, which, like its human cognate, specifically binds to CRK but not DRK/GRB2 adaptor molecules. During Drosophila development, constitutive membrane binding of C3G, which also occurs during v-crk transformation, results in cell fate changes and overproliferation, mimicking overactivity of the RAS-MAPK pathway. The effects of C3G overactivity can be suppressed by reducing the gene dose of components of the RAS-MAPK pathway and of RAP1. These findings provide the first in vivo evidence that membrane localization of C3G can trigger activation of RAP1 and RAS resulting in the activation of MAPK, one of the hallmarks of v-crk transformation previously thought to be mediated through activation of SOS.

MeSH Terms
Amino Acid Sequence Animals Animals, Genetically Modified Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Division Chromosome Mapping DNA Primers/genetics Drosophila/cytology,growth & development,metabolism Eye/growth & development,metabolism GTP-Binding Proteins/metabolism Gene Expression Regulation, Developmental Guanine Nucleotide Exchange Factors Humans Insect Proteins/genetics,metabolism Molecular Sequence Data Oncogene Protein v-crk Proteins/genetics,metabolism Retroviridae Proteins, Oncogenic/metabolism Signal Transduction Wings, Animal/growth & development,metabolism rap GTP-Binding Proteins ras Guanine Nucleotide Exchange Factors ras Proteins/metabolism
Chemicals
DNA Primers Guanine Nucleotide Exchange Factors Insect Proteins Oncogene Protein v-crk Proteins Retroviridae Proteins, Oncogenic ras Guanine Nucleotide Exchange Factors Calcium-Calmodulin-Dependent Protein Kinases GTP-Binding Proteins rap GTP-Binding Proteins ras Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ishimaru S
Laboratory of Molecular Oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Williams R
Clark E
Hanafusa H
Gaul U
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.1.145
Published
1999-01-04
Pages
145-55
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171110
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/18.1.145 PMC Full Text View journal details
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