MET activates RAS signaling

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

Activated MET receptor recruits the RAS guanyl nucleotide exchange factor (GEF) SOS1 indirectly, either through the GRB2 adapter (Ponzetto et al. 1994, Fournier et al. 1996, Shen and Novak 1997, Besser et al. 1997), GAB1 (Weidner et al. 1996) or SHC1 and GRB2 (Pelicci et al. 1995), or RANBP9 (Wang et al. 2002, Wang et al. 2004). Association of SOS1 with the activated MET receptor complex leads to exchange of GDP to GTP on RAS and activation of RAS signaling (Pelicci et al. 1995, Besser et al. 1997, Shen and Novak 1997, Wang et al. 2004).
PTPN11 (SHP2) may contribute to activation of RAS signaling downstream of MET (Schaeper et al. 2000, Furcht et al. 2014).
Sustained activation of MAPK1 (ERK2) and MAPK3 (ERK1) downstream of MET-activated RAS may require MET endocytosis and signaling from endosomes (Peschard et al. 2001, Hammond et al. 2001, Petrelli et al. 2002, Kermorgant and Parker 2008).
Binding of MET to MUC20 or RANBP10 interferes with RAS activation (Higuchi et al. 2004, Wang et al. 2004).

Literature References
PubMed ID Title Journal Year
15314156 MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met Mol. Cell. Biol. 2004
8703035 Branching tubulogenesis but not scatter of madin-darby canine kidney cells requires a functional Grb2 binding site in the Met receptor tyrosine kinase J. Biol. Chem. 1996
11741535 Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein Mol. Cell 2001
9038378 Regulation of the urokinase-type plasminogen activator gene by the oncogene Tpr-Met involves GRB2 Oncogene 1997
24951116 Multivariate signaling regulation by SHP2 differentially controls proliferation and therapeutic response in glioma cells J. Cell. Sci. 2014
11420688 Down-regulation of MET, the receptor for hepatocyte growth factor Oncogene 2001
8906793 Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis Nature 1996
18779368 Receptor trafficking controls weak signal delivery: a strategy used by c-Met for STAT3 nuclear accumulation J. Cell Biol. 2008
9070211 DDT stimulates c-erbB2, c-met, and STATS tyrosine phosphorylation, Grb2-Sos association, MAPK phosphorylation, and proliferation of human breast epithelial cells Biochem. Biophys. Res. Commun. 1997
10871282 Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses J. Cell Biol. 2000
7513258 A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family Cell 1994
12147692 Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM J. Biol. Chem. 2002
14684163 A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling Biochem. Biophys. Res. Commun. 2004
11894096 The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met Nature 2002
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