PMID- 21782801 OWN - NLM STAT- MEDLINE DCOM- 20111014 LR - 20161125 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 411 IP - 4 DP - 2011 Aug 12 TI - Degradation of the GAB1 adaptor by the ubiquitin-proteasome pathway hampers HGF/SF-MET signaling. PG - 780-5 LID - 10.1016/j.bbrc.2011.07.024 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Goormachtigh, Gautier AU - Goormachtigh G AD - CNRS UMR, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, France. FAU - Ji, Zongling AU - Ji Z FAU - Le Goff, Arnaud AU - Le Goff A FAU - Fafeur, Veronique AU - Fafeur V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110718 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (GAB1 protein, human) RN - 0 (HGF protein, human) RN - 0 (Receptors, Growth Factor) RN - 0 (Ubiquitin) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) RN - EC 6.3.2.- (CBL protein, human) SB - IM MH - Adaptor Proteins, Signal Transducing/*metabolism MH - HEK293 Cells MH - HeLa Cells MH - Hepatocyte Growth Factor/*metabolism MH - Humans MH - Proteasome Endopeptidase Complex/*metabolism MH - Proto-Oncogene Proteins c-cbl/metabolism MH - Proto-Oncogene Proteins c-met/*metabolism MH - Receptors, Growth Factor/*metabolism MH - Signal Transduction MH - Ubiquitin/metabolism MH - *Ubiquitination EDAT- 2011/07/26 06:00 MHDA- 2011/10/15 06:00 CRDT- 2011/07/26 06:00 PHST- 2011/07/04 00:00 [received] PHST- 2011/07/06 00:00 [accepted] PHST- 2011/07/26 06:00 [entrez] PHST- 2011/07/26 06:00 [pubmed] PHST- 2011/10/15 06:00 [medline] AID - S0006-291X(11)01243-5 [pii] AID - 10.1016/j.bbrc.2011.07.024 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2011 Aug 12;411(4):780-5. doi: 10.1016/j.bbrc.2011.07.024. Epub 2011 Jul 18.