CNRS UMR, Institut de Biologie de Lille, Université Lille-Nord de France, Institut Pasteur de Lille, France.
Biochem Biophys Res Commun. 2011 Aug 12;411(4):780-5. doi: 10.1016/j.bbrc.2011.07.024. Epub 2011 Jul 18.
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.
GRB2 相关衔接蛋白 1（GAB1）是一种重要的衔接蛋白/衔接物，可传递由肝细胞生长因子/分散因子（HGF/SF）激活的 MET 酪氨酸激酶受体的细胞内信号。我们发现，在对 HGF/SF 进行数小时的处理后，GAB1 蛋白水平通过涉及 MET 活性和蛋白酶体机制的降解机制发生降解。我们还表明，GAB1 以 CBL 依赖的方式被多泛素化。长期暴露于 HGF/SF 导致 GAB1 的下调比 MET 更持久，与 ERK MAP 激酶对随后的急性配体处理的重新激活的丧失相关。这些数据表明 GAB1 被 CBL 泛素化并被蛋白酶体降解，并在 HGF/SF-MET 信号的负反馈调节中发挥作用。
