Identification of Rap 1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G

Takaya Gotoh, Seisuke Hattori, Shun Nakamura, Hitoshi Kitayama, Makoto Noda, Yoshimi Takai, Kozo Kaibuchi, Hideki Matsui, Osamu Hatase, Hidehiro Takahashi, Takeshi Kurata, Michiyuki Matsuda

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Abstract

C3G, which was identified as a Crk SH3 domain-binding guanine nucleotide-releasing factor, shows sequence similarity to CDC25 and Sos family proteins (S. Tanaka, T. Morishita, Y. Hashimoto, S. Hattori, S. Nakamura, M. Shibuya, K. Matuoka, T. Takenawa, T. Kurata, K. Nagashima, and M. Matsuda, Proc. Natl. Acad. Sci. USA 91:3443-3447, 1994). The substrate specificity of C3G was examined by in vitro and in vivo experiments. C3G markedly stimulated dissociation of bound GDP from Rap1B but marginally affected the same reaction of other Ras family proteins (Ha-Ras, N-Ras, and RalA). C3G also stimulated binding of GTP-γS [guanosine 5′-3-O-(thio)triphosphate] to Rap1B. When C3G and RaplA were expressed in COS7 cells, marked accumulation of the active GTP-bound form of Rap1A was observed, while Sos was not effective in the activation of RaplA. These results clearly show that C3G is an activator for Rapl. Furthermore, expression of C3G with a membrane localization signal in a v-Ki-ras transformant, DT, induced a reversion of the cells to the flat form, possibly through the activation of endogenous Rap1.

Original languageEnglish
Pages (from-to)6746-6753
Number of pages8
JournalMolecular and Cellular Biology
Volume15
Issue number12
DOIs
Publication statusPublished - Dec 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Gotoh, T., Hattori, S., Nakamura, S., Kitayama, H., Noda, M., Takai, Y., Kaibuchi, K., Matsui, H., Hatase, O., Takahashi, H., Kurata, T., & Matsuda, M. (1995). Identification of Rap 1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G. Molecular and Cellular Biology, 15(12), 6746-6753. https://doi.org/10.1128/MCB.15.12.6746