The Sos1-Rac1 signaling: Possible involvement of a vacuolar H +-ATPase E subunit

Koichi Miura, Shoko Miyazawa, Shuichi Furuta, Junji Mitsushita, Keiju Kamijo, Hiroshi Ishida, Toru Miki, Kazumi Suzukawa, James Resaull, Terry D. Copeland, Tohru Kamata

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27 Citations (Scopus)

Abstract

We have purified and identified a 32-kDa protein interacting with the Dbl oncogene homology domain of mSos1(Sos-DH) from rat brains by glutathione S-transferase-Sos-DH affinity chromatography. Peptide sequencing revealed that the protein is identical to a positive regulatory E subunit (V-ATPase E) of a vacuolar H+-ATPase, which is responsible for acidification of endosome and alkalinization of intracellular pH. The interaction between V-ATPase E and Sos-DH was confirmed by yeast two-hybrid assay. A coimmunoprecipitation assay demonstrated that a V-ATPase E protein physiologically bound to mSos1, and the protein was colocalized with mSos1 in the cytoplasm, as determined by immunohistochemistry. mSos1 was found in the early endosome fraction together with V-ATPase E and Rac1, suggesting the functional involvement of mSos1/V-ATPase E complexes in the Rac1 activity at endosomes. Overexpression of V-ATPase E in COS cells enhanced the ability of mSos1 to promote the guanine nucleotide exchange activity for Rac1 and stimulated the kinase activity of Jun kinase, a downstream target of Rac1. Thus, the data indicate that V-ATPase E may participate in the regulation of the mSos1-dependent Rac1 signaling pathway involved in growth factor receptor-mediated cell growth control.

Original languageEnglish
Pages (from-to)46276-46283
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number49
DOIs
Publication statusPublished - 2001 Dec 7

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Miura, K., Miyazawa, S., Furuta, S., Mitsushita, J., Kamijo, K., Ishida, H., Miki, T., Suzukawa, K., Resaull, J., Copeland, T. D., & Kamata, T. (2001). The Sos1-Rac1 signaling: Possible involvement of a vacuolar H +-ATPase E subunit. Journal of Biological Chemistry, 276(49), 46276-46283. https://doi.org/10.1074/jbc.M102387200