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Cytoskeletal modification of Rho guanine nucleotide exchange factor activity: identification of a Rho guanine nucleotide exchange factor as a binding partner for Sept9b, a mammalian septin

Oncogene volume 24, pages 65–76 (2005)Cite this article

Abstract

Small GTPase Rho and septin family proteins are thought to be related to tumorigenesis. We have identified a Rho-guanine nucleotide exchange factor (GEF) as a binding partner for a mammalian septin Sept9b using yeast two-hybrid screening. We termed this molecule septin-associated RhoGEF (SA-RhoGEF). Molecular dissection analyses indicated that the C-terminal area of SA-RhoGEF exhibited binding to the N-terminal variable region of Sept9b. SA-RhoGEF was found by immunoprecipitation analysis to associate with septin complexes in REF52 fibroblast cells, maybe through direct interaction with Sept9b. Immunofluorescence analyses revealed the colocalization of SA-RhoGEF and Sept9b along with actin stress fibers in REF52 cells, and their colocalization along stress fibers was most likely to depend on their mutual interaction. In transient expression analyses, Sept9b inhibited SA-RhoGEF-dependent Rho activation in COS7 and HeLa cells. SA-RhoGEF and its fragments expressed in REF52 cells altered endogenous septin filament structures. To our knowledge, SA-RhoGEF is the first molecule providing a link between septins and Rho signaling.

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Abbreviations

GEF:

guanine nucleotide exchange factor

DH:

Dbl homology

PH:

pleckstrin homology

GST:

glutathione S-transferase

aa:

amino acid

nt:

nucleotide

RBD:

active Rho-binding domain of Rhotekin

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Acknowledgements

We thank N Saitoh, C Yuhara and I Iwamoto for technical assistance. We are grateful to M Ohara for language assistance and to Dr T Nagase (Kazusa DNA Inst., Japan) for providing KIAA0521 clone. KN thanks Drs T Asano (Inst. Dev. Res., Kasugai) and Y Nozawa (Gifu International Inst. of Biotechnol., Gifu) for encouragement. This work was supported in part by grants-in-aid for scientific research and for cancer research from Ministry of Education, Science, Technology, Sports and Culture of Japan, and by the grant from Yamanouchi Foundation for Research on Metabolic Disorders.

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  1. Koh-Ichi Nagata

    Present address: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, 480-0392, Japan

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  1. Division of Biochemistry, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Koh-Ichi Nagata & Masaki Inagaki

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Nagata, KI., Inagaki, M. Cytoskeletal modification of Rho guanine nucleotide exchange factor activity: identification of a Rho guanine nucleotide exchange factor as a binding partner for Sept9b, a mammalian septin. Oncogene 24, 65–76 (2005). https://doi.org/10.1038/sj.onc.1208101

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