TY - JOUR
T1 - Ras-Activated Endocytosis Is Mediated by the Rab5 Guanine Nucleotide Exchange Activity of RIN1
AU - Tall, Gregory G.
AU - Barbieri, M. Alejandro
AU - Stahl, Philip D.
AU - Horazdovsky, Bruce F.
N1 - Funding Information:
We thank Gray Pearson, Melanie Cobb, Mike White, and John Colicelli for many helpful discussions. In addition, we thank Michael Roth, Brian Davies, and Luis Mayorga for critical review of this manuscript. We would also like to acknowledge Dr. Ilya Frolov for his help in using the Sinrep5 virus and Libby Peters for her excellent technical assistance. This work was supported in part by Grants from the National Institute of Health (GM55301 to B.F.H and GM42259, AI35884, and AI20015 to P.D.S.)
PY - 2001/7
Y1 - 2001/7
N2 - 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.
AB - 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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U2 - 10.1016/S1534-5807(01)00008-9
DO - 10.1016/S1534-5807(01)00008-9
M3 - Article
C2 - 11703925
AN - SCOPUS:0035408008
SN - 1534-5807
VL - 1
SP - 73
EP - 82
JO - Developmental Cell
JF - Developmental Cell
IS - 1
ER -