STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif

被引：97

作者：

Mizuno, E ^{[1
]}

Kawahata, K ^{[1
]}

Kato, M ^{[1
]}

Kitamura, N ^{[1
]}

Komada, M ^{[1
]}

机构：

[1] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Sci Biol, Yokohama, Kanagawa 2268501, Japan

来源：

MOLECULAR BIOLOGY OF THE CELL | 2003年 / 14卷 / 09期

关键词：

D O I：

10.1091/mbc.E02-12-0823

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：3675 / 3689

页数：15

共 55 条

[1] The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways [J].