Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 411, Issue 4, Pages 780-785Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.07.024
Keywords
HGF/SF; MET; GAB1; Ubiquitin; CBL; Degradation
Categories
Funding
- CNRS
- Pasteur Institute of Lille
- Universite Lille-Nord de France
- INSERM
- Fondation de France
- Region Nord Pas de Calais
- Ligue Regionale Contre le Cancer-Comite du Nord et de l'Aisne
- French Ministere de la Recherche
- ARC (Association pour la Recherche contre le Cancer)
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The GRB2 associated binder 1 (GAB1) is an essential docking/adaptor protein for transmitting intracellular signals of the MET tyrosine kinase receptor activated by hepatocyte growth factor/scatter factor (HGF/SF). We found that in response to hours of HGF/SF treatment, the GAB1 protein level is degraded by a mechanism involving MET activity and the proteasomal machinery. We also showed that GAB1 is both multi- and poly-ubiquitinated in a CBL-dependent manner. A long term exposure to HGF/SF caused a more sustained down-regulation of GAB1 than of MET, associated with a loss of reactivation of the ERK MAP kinases to subsequent acute ligand treatment. These data demonstrate that GAB1 is ubiquitinated by CBL and degraded by the proteasome, and plays a role in negative-feedback regulation of HGF/SF-MET signaling. (C) 2011 Elsevier Inc. All rights reserved.
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