Degradation of the GAB1 adaptor by the ubiquitin-proteasome pathway hampers HGF/SF-MET signaling

Gautier Goormachtigh; Zongling Ji; Arnaud Le Goff; Véronique Fafeur

doi:10.1016/j.bbrc.2011.07.024

Degradation of the GAB1 adaptor by the ubiquitin-proteasome pathway hampers HGF/SF-MET signaling

Gautier Goormachtigh, Zongling Ji, Arnaud Le Goff, Véronique Fafeur

Research output: Contribution to journal › Article › peer-review

Abstract

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. © 2011 Elsevier Inc.

Original language	English
Pages (from-to)	780-785
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	411
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2011.07.024
Publication status	Published - 12 Aug 2011

Keywords

CBL
Degradation
GAB1
HGF/SF
MET
Ubiquitin

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10.1016/j.bbrc.2011.07.024

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title = "Degradation of the GAB1 adaptor by the ubiquitin-proteasome pathway hampers HGF/SF-MET signaling",

abstract = "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. {\textcopyright} 2011 Elsevier Inc.",

keywords = "CBL, Degradation, GAB1, HGF/SF, MET, Ubiquitin",

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AU - Goormachtigh, Gautier

AU - Ji, Zongling

AU - Le Goff, Arnaud

AU - Fafeur, Véronique

PY - 2011/8/12

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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. © 2011 Elsevier Inc.

KW - CBL

KW - Degradation

KW - GAB1

KW - HGF/SF

KW - MET

KW - Ubiquitin

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

Degradation of the GAB1 adaptor by the ubiquitin-proteasome pathway hampers HGF/SF-MET signaling

Abstract

Keywords

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