PMID- 22915589 OWN - NLM STAT- MEDLINE DCOM- 20121231 LR - 20240512 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 287 IP - 42 DP - 2012 Oct 12 TI - Anti-apoptotic role of caspase-cleaved GAB1 adaptor protein in hepatocyte growth factor/scatter factor-MET receptor protein signaling. PG - 35382-35396 LID - S0021-9258(20)62685-0 [pii] LID - 10.1074/jbc.M112.409797 [doi] AB - The GRB2-associated binder 1 (GAB1) docking/scaffold protein is a key mediator of the MET-tyrosine kinase receptor activated by hepatocyte growth factor/scatter factor (HGF/SF). Activated MET promotes recruitment and tyrosine phosphorylation of GAB1, which in turn recruits multiple proteins and mediates MET signaling leading to cell survival, motility, and morphogenesis. We previously reported that, without its ligand, MET is a functional caspase target during apoptosis, allowing the generation of a p40-MET fragment that amplifies apoptosis. In this study we established that GAB1 is also a functional caspase target by evidencing a caspase-cleaved p35-GAB1 fragment that contains the MET binding domain. GAB1 is cleaved by caspases before MET, and the resulting p35-GAB1 fragment is phosphorylated by MET upon HGF/SF binding and can interact with a subset of GAB1 partners, PI3K, and GRB2 but not with SHP2. This p35-GAB1 fragment favors cell survival by maintaining HGF/SF-induced MET activation of AKT and by hindering p40-MET pro-apoptotic function. These data demonstrate an anti-apoptotic role of caspase-cleaved GAB1 in HGF/SF-MET signaling. FAU - Le Goff, Arnaud AU - Le Goff A AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. FAU - Ji, Zongling AU - Ji Z AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France; Faculty of Life Sciences, C2222 Michael Smith Building, University of Manchester, Manchester, United Kingdom. FAU - Leclercq, Berenice AU - Leclercq B AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. FAU - Bourette, Roland P AU - Bourette RP AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. FAU - Mougel, Alexandra AU - Mougel A AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. FAU - Guerardel, Cateline AU - Guerardel C AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. FAU - de Launoit, Yvan AU - de Launoit Y AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. FAU - Vicogne, Jerome AU - Vicogne J AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. FAU - Goormachtigh, Gautier AU - Goormachtigh G AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. FAU - Fafeur, Veronique AU - Fafeur V AD - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, Institut Pasteur de Lille, IFR142, Lille, France. Electronic address: veronique.fafeur@ibl.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120822 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (GAB1 protein, human) RN - 0 (GRB2 Adaptor Protein) RN - 0 (GRB2 protein, human) RN - 0 (HGF protein, human) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.4.22.- (Caspases) SB - IM MH - Adaptor Proteins, Signal Transducing/genetics/*metabolism MH - Animals MH - Apoptosis/*physiology MH - Caspases/genetics/*metabolism MH - Dogs MH - Enzyme Activation/physiology MH - GRB2 Adaptor Protein/genetics/metabolism MH - HeLa Cells MH - Hep G2 Cells MH - Hepatocyte Growth Factor/genetics/*metabolism MH - Humans MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - *Proteolysis MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - Proto-Oncogene Proteins c-met/genetics/*metabolism MH - Signal Transduction/*physiology PMC - PMC3471683 EDAT- 2012/08/24 06:00 MHDA- 2013/01/01 06:00 PMCR- 2013/10/12 CRDT- 2012/08/24 06:00 PHST- 2012/08/24 06:00 [entrez] PHST- 2012/08/24 06:00 [pubmed] PHST- 2013/01/01 06:00 [medline] PHST- 2013/10/12 00:00 [pmc-release] AID - S0021-9258(20)62685-0 [pii] AID - M112.409797 [pii] AID - 10.1074/jbc.M112.409797 [doi] PST - ppublish SO - J Biol Chem. 2012 Oct 12;287(42):35382-35396. doi: 10.1074/jbc.M112.409797. Epub 2012 Aug 22.