Ras-Activated Endocytosis Is Mediated by the Rab5 Guanine Nucleotide Exchange Activity of RIN1

Gregory G. Tall, M. Alejandro Barbieri, Philip D. Stahl, Bruce F Horazdovsky

Research output: Contribution to journalArticle

211 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalDevelopmental Cell
Volume1
Issue number1
DOIs
StatePublished - Jul 2001
Externally publishedYes

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14-3-3 Proteins
Guanine Nucleotide Exchange Factors
Guanine Nucleotides
Endocytosis
Epidermal Growth Factor Receptor
Fusion reactions
Nucleotides
Endosomes
Catalytic Domain

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Ras-Activated Endocytosis Is Mediated by the Rab5 Guanine Nucleotide Exchange Activity of RIN1. / Tall, Gregory G.; Barbieri, M. Alejandro; Stahl, Philip D.; Horazdovsky, Bruce F.

In: Developmental Cell, Vol. 1, No. 1, 07.2001, p. 73-82.

Research output: Contribution to journalArticle

Tall, Gregory G. ; Barbieri, M. Alejandro ; Stahl, Philip D. ; Horazdovsky, Bruce F. / Ras-Activated Endocytosis Is Mediated by the Rab5 Guanine Nucleotide Exchange Activity of RIN1. In: Developmental Cell. 2001 ; Vol. 1, No. 1. pp. 73-82.
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