Reactome: A Curated Pathway Database

Negative regulation of MET activity

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

Signaling by MET receptor is negatively regulated mainly by MET receptor dephosphorylation or MET receptor degradation. Protein tyrosine phosphatase PTPRJ dephosphorylates MET tyrosine residue Y1349, thus removing the docking site for the GAB1 adapter (Palka et al. 2003). Protein tyrosine phosphatases PTPN1 and PTPN2 dephosphorylate MET tyrosines Y1234 and Y1235 in the kinase activation loop, thus attenuating catalytic activity of MET (Sangwan et al. 2008). The E3 ubiquitin ligase CBL promotes ubiquitination of the activated MET receptor and subsequent MET degradation. CBL contains a RING finger domain that engages E2 protein ubiquitin ligases to mediate ubiquitination of MET, which may occur at the cell membrane or in the early endocytic compartment. Ubiquitinated MET is degraded in a late endosomal or lysosomal compartment in a proteasome-dependent manner. The involvement of proteasome in MET degradation seems to be indirect, through an effect on MET endocytic trafficking (Jeffers et al. 1997, Peschard et al. 2001, Hammond et al. 2001, Petrelli et al. 2002). LRIG1 promotes lysosome-dependent degradation of MET in the absence of HGF-mediated activation (Lee et al. 2014, Oh et al. 2014).
MET-mediated activation of RAS signaling is inhibited by MET receptor binding to MUC20 (Higuchi et al. 2004) or RANBP10 (Wang et al. 2004).

Literature References
Participant Of
Orthologous Events
Cross References
BioModels Database