Reactome | EPS15 and HGS bind ubiquitinated MET

EPS15 and HGS bind ubiquitinated MET

Stable Identifier

R-HSA-8875490

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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EPS15 and HGS (Hrs) both bind MET receptor ubiquitinated by CBL upon HGF stimulation. EPS15 and HGS, which together form a ternary complex with STAM proteins (Bache et al. 2003) are involved in activated MET receptor endocytosis and degradation through the lysosomal route (Hammond et al. 2003). EPS15 can simultaneously interact with ubiquitinated MET and MET-bound GRB2 (Parachoniak et al. 2009). HGS also binds to ubiquitinated LRIG1 and is involved in LRIG1-trigerred lysosomal downregulation of MET in the absence of HGF stimulation (Oh et al. 2014). MET phosphorylates EPS15, HGS and STAM, but the functional significance of this phosphorylation for MET downregulation is not known (Row et al. 2005, Parachoniak et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
12686592	Endosomal dynamics of Met determine signaling output Hammond, DE, Carter, S, McCullough, J, Urbé, S, Vande Woude, G, Clague, MJ	Mol. Biol. Cell	2003
19109251	Distinct recruitment of Eps15 via Its coiled-coil domain is required for efficient down-regulation of the met receptor tyrosine kinase Parachoniak, CA, Park, M	J. Biol. Chem.	2009
15828871	Growth factors induce differential phosphorylation profiles of the Hrs-STAM complex: a common node in signalling networks with signal-specific properties Row, PE, Clague, MJ, Urbé, S	Biochem. J.	2005
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
12551915	STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes Bache, KG, Raiborg, C, Mehlum, A, Stenmark, H	J. Biol. Chem.	2003