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 journalArticlepeer-review

218 Scopus citations


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
Issue number1
StatePublished - Jul 2001

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology


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