The Journal of Membrane Biology

, Volume 245, Issue 8, pp 495–506

Coregulation of Multiple Signaling Mechanisms in pp60v-Src-Induced Closure of Cx43 Gap Junction Channels

Authors

  • Siddhartha S. Mitra
    • Department of BiochemistryUniversity of Texas Health Science Center at San Antonio
    • Institute of Stem Cell Biology and Regenerative MedicineStanford University
  • Ji Xu
    • Department of BiochemistryUniversity of Texas Health Science Center at San Antonio
    • Department of Physiology, David Geffen School of MedicineUniversity of California Los Angeles
    • Department of BiochemistryUniversity of Texas Health Science Center at San Antonio
Article

DOI: 10.1007/s00232-012-9500-0

Cite this article as:
Mitra, S.S., Xu, J. & Nicholson, B.J. J Membrane Biol (2012) 245: 495. doi:10.1007/s00232-012-9500-0

Abstract

Attenuation in gap junctional coupling has consistently been associated with induction of rapid or synchronous cell division in normal and pathological conditions. In the case of the v-src oncogene, gating of Cx43 gap junction channels has been linked to both direct phosphorylation of tyrosines (Y247 and 265) and phosphorylation of the serine targets of Erk1/2 (S255, 279 and 282) on the cytoplasmic C-terminal domain of Cx43. However, only the latter has been associated with acute, rather than chronic, gating of the channels immediately after v-src expression, a process that is mediated through a “ball-and-chain” mechanism. In this study we show that, while ERK1/2 is necessary for acute closure of gap junction channels, it is not sufficient. Rather, multiple pathways converge to regulate Cx43 coupling in response to expression of v-src, including parallel signaling through PKC and MEK1/2, with additional positive and negative regulatory effects mediated by PI3 kinase, distinguished by the involvement of Akt.

Keywords

Cx43Gap junctionv-SrcErk1/2Signal transduction

Copyright information

© Springer Science+Business Media, LLC 2012