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v-Src requires Ras signaling for the suppression of gap junctional intercellular communication

Oncogene volume 25, pages 2420–2424 (2006)Cite this article

Abstract

Cell transformation by v-Src causes suppression of gap junctional intercellular communication (GJIC). Although tyrosine phosphorylation of connexin43 (Cx43), a gap junctional component, appears to be necessary for the suppression, involvement of other signaling remains unclear. We investigated the role of Ras signaling in the suppression of GJIC by v-Src. Conditional expression of either S17N Ras or mtGap1m dramatically recovered GJIC in v-Src-transformed cells. Although expression of S17N Ras or mtGap1m substantially decreased the levels of active Ras, tyrosine phosphorylation of cellular proteins including Cx43 remained unchanged. Similarly, treatment of v-Src-transfomed cells with a Ras farnesyltransferase inhibitor, manumycin A, restored GJIC, whereas tyrosine phosphorylation of Cx43 remained unchanged. Thus, these results strongly suggest that, in addition to Cx43 phosphorylation, constitutive activation of Ras signaling is required for the suppression of GJIC by v-Src.

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References

  • Atkinson MM, Menko AS, Johnson RG, Sheppard JR, Sheridan JD . (1981). J Cell Biol 91: 573–578.

  • Atkinson MM, Sheridan J . (1984). J Cell Biol 99: 401a.

  • Bromberg JF, Horvath CM, Besser D, Lathem WW, Darnell Jr JE . (1998). Mol Cell Biol 5: 2553–2558.

  • Cameron SJ, Malik S, Akaike M, Lerner-Marmarosh N, Yan C, Lee JD et al. (2003). J Biol Chem 278: 18682–18688.

  • Campbell SL, Khosrvi-Far R, Rossman KL, Clark GJ, Der CJ . (1998). Oncogene 17: 1395–1413.

  • Cao X, Tay A, Guy GR, Tan YH . (1996). Mol Cell Biol 16: 1595–1603.

  • Cottrell GT, Lin R, Warn-Cramer BJ, Lau AF, Burt JM . (2003). Am J Physiol Cell Physiol 284: 511–520.

  • DeClue JE, Zhang K, Redford P, Vass WC, Lowy DR . (1991). Mol Cell Biol 11: 2819–2825.

  • Egan SE, Weinberg RA . (1993). Nature 365: 781–783.

  • Evans WH, Martin PE . (2002). Mol Membr Biol 19: 121–136.

  • Feig LA, Cooper GM . (1988). Mol Cell Biol 8: 3235–3243.

  • Goodenough DA, Goliger JA, Paul DL . (1996). Annu Rev Biochem 65: 475–502.

  • Hamaguchi M, Matsuyoshi N, Ohnishi Y, Gotoh B, Takeichi M, Nagai Y . (1993). EMBO J 12: 307–314.

  • Hara M, Akasaka K, Akinaga S, Okabe M, Nakano H, Gomez R et al. (1993). Proc Natl Acad Sci USA 90: 2281–2285.

  • Lampe PD, Lau AF . (2004). Int J Biochem Cell Biol 36: 1171–1186.

  • Lin R, Warn-Cramer BJ, Kurata WE, Lau AF . (2001). J Cell Biol 154: 815–827.

  • Loewenstein WR . (1981). Physiol Rev 61: 829–913.

  • Maekawa M, Li S, Iwamatsu A, Morishita T, Yokota K, Imai Y et al. (1994). Mol Cell Biol 10: 6879–6885.

  • Nori M, Vogel US, Gibbs JB, Weber MJ . (1991). Mol Cell Biol 11: 2812–2818.

  • Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC . (2003). Physiol Rev 83: 1359–1400.

  • Smith MR, DeGudicibus SJ, Stacey DW . (1986). Nature 320: 540–543.

  • Swenson KI, Piwnica-Worms H, McNamee H, Paul DL . (1990). Cell Regul 1: 989–1002.

  • Turkson J, Bowman T, Adnane J, Zhang Y, Djeu JY, Sekharam M et al. (1999). Mol Cell Biol 19: 7519–7528.

  • Vanhamme L, Rolin S, Szpirer C . (1989). Exp Cell Res 180: 297–301.

  • Warn-Cramer BJ, Lampe PD, Kurata WE, Kanemitsu MY, Loo LW, Eckhart W et al. (1996). J Biol Chem 271: 3779–3786.

  • Warn-Cramer BJ, Lau AF . (2004). Biochim Biophys Acta 1662: 81–95.

  • Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J et al. (1995). Science 269: 81–83.

  • Zhou L, Kasperek EM, Nicholson BJ . (1999). J Cell Biol 144: 1033–1045.

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Acknowledgements

We thank members of the Hamaguchi laboratory for their helpful discussions. This work was supported by a Grant-in-Aid for COE research from the Ministry of Education, Science and Culture of Japan.

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Authors and Affiliations

  1. Division of Cancer Biology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    S Ito, Y Ito, T Senga & M Hamaguchi

  2. Division of Clinical Immunology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    S Ito & S Matsuo

  3. Division of Cellular Genome Proteomics, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan

    S Hattori

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  1. S Ito
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Correspondence to M Hamaguchi.

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Ito, S., Ito, Y., Senga, T. et al. v-Src requires Ras signaling for the suppression of gap junctional intercellular communication. Oncogene 25, 2420–2424 (2006). https://doi.org/10.1038/sj.onc.1209263

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