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

作者：Goormachtigh Gautier; Ji Zongling; Le Goff Arnaud; Fafeur Veronique^*

来源：Biochemical and Biophysical Research Communications, 2011, 411(4): 780-785.

DOI：10.1016/j.bbrc.2011.07.024

• HGF/SF
• MET
• GAB1
• Ubiquitin
• CBL
• Degradation

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.

• 出版日期2011-8-12