MET activates RAS signaling

Summary
Organism
Homo sapiens (human)
Reactome
R-HSA-8851805
PubChem
R-HSA-8851805
Description
  • 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).
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
Displaying all 8 entries
UniProt ID Protein Name Gene Symbol Pathway Viewer
P01111 GTPase NRas
  • HRAS1
  • NRAS
view
P01112 GTPase HRas
  • HRAS
  • HRAS1
view
P08581 Hepatocyte growth factor receptor
  • MET
view
P14210 Hepatocyte growth factor
  • HGF
  • HPTA
view
Q07889 Son of sevenless homolog 1
  • SOS1
view
Q6VN20 Ran-binding protein 10
  • KIAA1464
  • RANBP10
view
Q8N307 Mucin-20
  • KIAA1359
  • MUC20
  • UNQ2782/PRO7170
view
Q96S59 Ran-binding protein 9
  • RANBP9
  • RANBPM
view

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Acknowledgements

Supported by JST NBDC Grant Number JPMJND2204

Partly supported by NIH Common Fund Grant #1U01GM125267-01


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Last updated: April 6, 2026