Reactome | MET activates RAS signaling

MET activates RAS signaling

Stable Identifier

R-HSA-8851805

Type

Pathway

Species

Homo sapiens

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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
11894096	The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met Gilestro, GF, Migone, N, Lanzardo, S, Giordano, S, Comoglio, PM, Petrelli, A	Nature	2002
14684163	A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling Wang, D, Schoen, SR, Li, Z, Messing, EM, Wu, G	Biochem. Biophys. Res. Commun.	2004
12147692	Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM Wang, D, Li, Z, Messing, EM, Wu, G	J. Biol. Chem.	2002
7513258	A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family Bardelli, A, Comoglio, PM, Zhen, Z, Ponzetto, C, Giordano, S, dalla Zonca, P, Maina, F, Panayotou, G, Graziani, A	Cell	1994
10871282	Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses Kempkes, B, Fuchs, KP, Birchmeier, W, Sachs, M, Gehring, NH, Schaeper, U	J. Cell Biol.	2000
9070211	DDT stimulates c-erbB2, c-met, and STATS tyrosine phosphorylation, Grb2-Sos association, MAPK phosphorylation, and proliferation of human breast epithelial cells Shen, K, Novak, RF	Biochem. Biophys. Res. Commun.	1997
18779368	Receptor trafficking controls weak signal delivery: a strategy used by c-Met for STAT3 nuclear accumulation Kermorgant, S, Parker, PJ	J. Cell Biol.	2008
8906793	Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis Brinkmann, V, Behrens, J, Birchmeier, W, Weidner, KM, Sachs, M, Di Cesare, S	Nature	1996
11420688	Down-regulation of MET, the receptor for hepatocyte growth factor Urbé, S, Clague, MJ, Hammond, DE, Vande Woude, GF	Oncogene	2001
24951116	Multivariate signaling regulation by SHP2 differentially controls proliferation and therapeutic response in glioma cells Lazzara, MJ, Furcht, CM, Mathew, LK, Simon, MC, Muñoz Rojas, AR, Skuli, N, Buonato, JM	J. Cell. Sci.	2014
9038378	Regulation of the urokinase-type plasminogen activator gene by the oncogene Tpr-Met involves GRB2 Bardelli, A, Comoglio, PM, Besser, D, Thelen, M, Nagamine, Y, Ponzetto, C, Didichenko, S	Oncogene	1997
11741535	Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein Band, H, Peschard, P, Naujokas, MA, Fournier, TM, Park, M, Lamorte, L, Langdon, WY	Mol. Cell	2001
15314156	MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met Nakamura, M, Orita, T, Li, H, Akiyama, K, Yamasaki, Y, Higuchi, T, Katsuya, K, Saito, Y, Yamamoto, T	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 Fournier, TM, Kamikura, D, Teng, K, Park, M	J. Biol. Chem.	1996