期刊
DEVELOPMENTAL CELL
卷 1, 期 1, 页码 73-82出版社
CELL PRESS
DOI: 10.1016/S1534-5807(01)00008-9
关键词
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资金
- NIAID NIH HHS [AI20015, AI35884] Funding Source: Medline
- NIGMS NIH HHS [GM42259, GM55301] Funding Source: Medline
RIN1 was originally identified by its ability to inhibit activated Ras and likely participates in multiple signaling pathways because it binds c-ABL and 14-3-3 proteins, in addition to Ras. RIN1 also contains a region homologous to the catalytic domain of Vps9p-like Rab guanine nucleotide exchange factors (GEFs). Here, we show that this region is necessary and sufficient for RIN1 interaction with the GDP-bound Rabs, Vps21p, and Rab5A. RIN1 is also shown to stimulate Rab5 guanine nucleotide exchange, Rab5A-dependent endosome fusion, and EGF receptor-mediated endocytosis. The stimulatory effect of RIN1 on all three of these processes is potentiated by activated Ras. We conclude that Ras-activated endocytosis is facilitated, in part, by the ability of Ras to directly regulate the Rab5 nucleotide exchange activity of RIN1.
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