Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CHO Cells
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Catalytic Domain
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Cricetinae
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Endocytosis / physiology*
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Endosomes / physiology
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Fibroblasts
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Fungal Proteins / chemistry
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Gene Expression / physiology
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Guanine Nucleotide Exchange Factors
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins
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Mice
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Saccharomyces cerevisiae Proteins*
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Vesicular Transport Proteins*
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rab GTP-Binding Proteins*
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rab5 GTP-Binding Proteins / metabolism*
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ras Proteins / metabolism*
Substances
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Carrier Proteins
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Fungal Proteins
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Guanine Nucleotide Exchange Factors
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Intracellular Signaling Peptides and Proteins
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Rin1 protein, mouse
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Saccharomyces cerevisiae Proteins
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VPS9 protein, S cerevisiae
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Vesicular Transport Proteins
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rab GTP-Binding Proteins
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rab5 GTP-Binding Proteins
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ras Proteins