STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif
STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif
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DOI：
10.1091/mbc.e02-12-0823
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发表时间：
2003-09-01
影响因子：
3.3
通讯作者：
Komada, M
中科院分区：
文献类型：
--
作者：
Mizuno, E;Kawahata, K;Komada, M
与泛素的缀合充当内体处的内吞和生物合成途径中的蛋白质的分选信号。信号转导衔接分子（STAM）蛋白，STAM 1和STAM 2，与肝细胞生长因子调节底物（Hrs），但他们的功能仍然未知。在此，我们表明，STAM蛋白结合泛素和泛素化的蛋白质和串联定位的VHS（Vps 27/Hrs/STAM）结构域和泛素相互作用基序作为结合位点（S）。STAM蛋白与早期内体上的Hrs共定位。STAM蛋白的过表达，而不是它们的突变体缺乏泛素结合活性，导致早期内体上的泛素化蛋白和配体激活的表皮生长因子受体的积累。这些结果表明，通过与早期内体上的泛素化货物蛋白的相互作用，通过VHS结构域和泛素相互作用基序，STAM蛋白参与货物蛋白的分选运输到溶酶体。
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.