Abstract
Conjugation with ubiquitin acts as a sorting signal for proteins in the endocytic and biosynthetic pathways at the endosome. Signal-transducing adaptor molecule (STAM) proteins, STAM1 and STAM2, are associated with hepatocyte growth factor-regulated substrate (Hrs) but their function remains unknown. Herein, we show that STAM proteins bind ubiquitin and ubiquitinated proteins and that the tandemly located VHS (Vps27/Hrs/STAM) domain and ubiquitin-interacting motif serve as the binding site(s). STAM proteins colocalize with Hrs on the early endosome. Overexpression of STAM proteins, but not their mutants lacking the ubiquitin-binding activity, causes the accumulation of ubiquitinated proteins and ligand-activated epidermal growth factor receptor on the early endosome. These results suggest that through interaction with ubiquitinated cargo proteins on the early endosome via the VHS domain and ubiquitin-interacting motif, STAM proteins participate in the sorting of cargo proteins for trafficking to the lysosome.
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Dates
Type | When |
---|---|
Created | 22 years, 2 months ago (June 16, 2003, 8:35 p.m.) |
Deposited | 4 years, 2 months ago (June 7, 2021, 11:30 a.m.) |
Indexed | 3 months, 1 week ago (May 28, 2025, 5:46 p.m.) |
Issued | 22 years ago (Sept. 1, 2003) |
Published | 22 years ago (Sept. 1, 2003) |
Published Print | 22 years ago (Sept. 1, 2003) |
@article{Mizuno_2003, title={STAM Proteins Bind Ubiquitinated Proteins on the Early Endosome via the VHS Domain and Ubiquitin-interacting Motif}, volume={14}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e02-12-0823}, DOI={10.1091/mbc.e02-12-0823}, number={9}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Mizuno, Emi and Kawahata, Kensuke and Kato, Masaki and Kitamura, Naomi and Komada, Masayuki}, year={2003}, month=sep, pages={3675–3689} }