MET binds LRIG1

Stable Identifier
R-HSA-8875374
Type
Reaction
Species
Homo sapiens
Compartment
plasma membrane
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Summation

LRIG1 can bind the MET receptor in the absence of HGF-mediated MET activation and trigger MET downregulation in a CBL-independent manner (Shattuck et al. 2007). MET targeting by the therapeutic antibody SAIT301 leads to LRIG1-mediated MET degradation through the lysosomal route. LRIG1-mediated MET downregulation requires ubiquitination of LRIG1 by an unknown ubiquitin ligase and can be inhibited by the ubiqitin hydrolase USP8, which deubiquitinates LRIG1 (Oh et al. 2014, Lee et al. 2014). Ubiquitinated LRIG1 binds to HGS (Hrs), a protein involved in clathrin-mediated endocytosis, and LRIG1 and MET co-localize with the lysosomal marker LAMP1 (Oh et al. 2014).

Literature References
PubMed ID Title Journal Year
17178829 LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy

Shattuck, DL, Miller, JK, Laederich, M, Funes, M, Petersen, H, Carraway, KL, Sweeney, C

Mol. Cell. Biol. 2007
23208509 Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody

Lee, JM, Kim, B, Lee, SB, Jeong, Y, Oh, YM, Song, YJ, Jung, S, Choi, J, Lee, S, Cheong, KH, Kim, DU, Park, HW, Han, YK, Kim, GW, Choi, H, Song, PH, Kim, KA

Oncogene 2014
24828152 USP8 modulates ubiquitination of LRIG1 for Met degradation

Oh, YM, Lee, SB, Choi, J, Suh, HY, Shim, S, Song, YJ, Kim, B, Lee, JM, Oh, SJ, Jeong, Y, Cheong, KH, Song, PH, Kim, KA

Sci Rep 2014
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Orthologous Events
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Authored
Orlic-Milacic, M  (2016-06-14)
Reviewed
Heynen, G  (2016-07-11)
Birchmeier, W  (2016-07-11)