The Met Receptor Degradation Pathway

Stephanie Carter, Sylvie Urbé, Michael J. Clague
2004 Journal of Biological Chemistry  
Acute stimulation of the receptor for the hepatocyte growth factor/scatter factor Met leads to receptor ubiquitination and down-regulation through the lysosomal degradation pathway. We have determined that the Met receptor undergoes multiple monoubiquitination as opposed to the appendage of polyubiquitin chains. Nevertheless, overexpression of ubiquitin in HEK293T cells enhances the rate of Met receptor degradation, in contrast to a point mutant of ubiquitin (K48R) that cannot form Lys 48
more » ... d polyubiquitin chains. Furthermore, an enhancement of Met degradation is also seen under conditions where the proteasome is inhibited by lactacystin. We propose that this reflects polyubiquitin-dependent sorting of Met, as the overexpression of ubiquitin but not K48R ubiquitin also restores hepatocyte growth factor-dependent phosphorylation of the endosomal coat protein Hrs from inhibition by lactacystin. Our data indicate a requirement for K48-R-linked polyubiquitin for Met endosomal trafficking independent of its canonical function of targeting for proteasomal degradation.
doi:10.1074/jbc.m407769200 pmid:15466866 fatcat:xwniweocfzbxvl7jn3tzjhzs6i