EPS15 and HGS bind ubiquitinated MET

Stable Identifier
R-HSA-8875490
Type
Reaction [binding]
Species
Homo sapiens
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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
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
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
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
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