Reactome | MET binds LRIG1

MET binds LRIG1

Stable Identifier

R-HSA-8875374

Type

Reaction

Species

Homo sapiens

Compartment

plasma membrane

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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
23208509	Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody Lee, JM, Kim, KA, Song, YJ, Han, YK, Jeong, Y, Choi, J, Lee, S, Choi, H, Cheong, KH, Kim, B, Oh, YM, Lee, SB, Song, PH, Jung, S, Kim, DU, Kim, GW, Park, HW	Oncogene	2014
17178829	LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy Sweeney, C, Funes, M, Petersen, H, Miller, JK, Shattuck, DL, Laederich, M, Carraway, KL	Mol. Cell. Biol.	2007
24828152	USP8 modulates ubiquitination of LRIG1 for Met degradation Shim, S, Kim, KA, Lee, JM, Oh, SJ, Choi, J, Cheong, KH, Suh, HY, Oh, YM, Song, PH, Song, YJ, Lee, SB, Kim, B, Jeong, Y	Sci Rep	2014