Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation
Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation
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DOI：
10.1016/j.bbrc.2003.08.078
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发表时间：
2003-10-03
影响因子：
3.1
通讯作者：
Sugamura, K
中科院分区：
文献类型：
--
作者：
Kanazawa, C;Morita, E;Sugamura, K
STAM家族蛋白，STAM 1和STAM 2/EAST/Hbp，是含有SH 3结构域和泛素相互作用基序的磷酸酪氨酸蛋白。它们的酵母同源物Hse 1及其结合蛋白Vps 27参与了液泡膜运输机制。在这里，我们表明，STAM I和STAM 2定位于内体膜。这些复合物中的一些含有Eps 15，一种内吞蛋白，其在Vps 4-A（一种AAA型ATP酶）的显性负性形式表达时聚集成团，Vps 4-A是正常内体功能所需的。这些结果支持了STAM是哺乳动物液泡蛋白分选（Vps）蛋白的观点。我们还证明，配体介导的表皮生长因子受体（EGFR）的降解是部分但不完全受损的Hrs（-/-）和STAM 1（-/-）STAM 2（-/-）小鼠胚胎成纤维细胞。此外，在Hrs（-/-）和STAM 1（-/-）STAM 2（-/-）细胞中均观察到内体肿胀。这些结果表明，STAMs和Hrs在哺乳动物内体/液泡蛋白分选途径中发挥重要作用。(C)2003年爱思唯尔公司All rights reserved.
The STAM family proteins, STAM1 and STAM2/EAST/Hbp, are phosphotyrosine proteins that contain SH3 domains and ubiquitin-interacting motifs. Their yeast homologue, Hse1, and its binding protein, Vps27, are involved in the vacuolar membrane transport machinery. Here we show that STAM I and STAM2 are localized to the endosomal membrane. Some of these complexes contain Eps15, an endocytic protein, which accumulates in clumps upon expression of a dominant-negative form of Vps4-A, an AAA-type ATPase, that is required for normal endosome function. These results support the idea that the STAMs are mammalian vacuolar protein sorting (Vps) proteins. We also demonstrate that ligand-mediated epidermal growth factor receptor (EGFR) degradation is partially but not completely impaired in both Hrs(-/-) and STAM1(-/-)STAM2(-/-) mouse embryonic fibroblasts. Furthermore, endosome swelling is seen in both Hrs(-/-) and STAM1(-/-)STAM2(-/-) cells. These results suggest that the STAMs and Hrs play important roles in the mammalian endosomal/vacuolar protein sorting pathway. (C) 2003 Elsevier Inc. All rights reserved.