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Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS–MAPK pathway and RAP1
Author(s) -
Ishimaru Satoshi,
Williams Rosemary,
Clark Elizabeth,
Hanafusa Hidesaburo,
Gaul Ulrike
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.1.145
Subject(s) - biology , rap1 , mapk/erk pathway , microbiology and biotechnology , cell growth , signal transduction , cell fate determination , genetics , guanine nucleotide exchange factor , gene , transcription factor
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.