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

First Author  Miura K Year  2001
Journal  J Biol Chem Volume  276
Issue  49 Pages  46276-83
PubMed ID  11560919 Mgi Jnum  J:73177
Mgi Id  MGI:2154655 Doi  10.1074/jbc.M102387200
Citation  Miura K, et al. (2001) The Sos1-Rac1 signaling. Possible involvement of a vacuolar H(+)-ATPase E subunit. J Biol Chem 276(49):46276-83
abstractText  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.
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