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



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.


Cx43 Gap junction v-Src Erk1/2 Signal transduction 

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Siddhartha S. Mitra
    • 1
    • 2
  • Ji Xu
    • 1
    • 3
  • Bruce J. Nicholson
    • 1
  1. 1.Department of BiochemistryUniversity of Texas Health Science Center at San AntonioSan AntonioUSA
  2. 2.Institute of Stem Cell Biology and Regenerative MedicineStanford UniversityStanfordUSA
  3. 3.Department of Physiology, David Geffen School of MedicineUniversity of California Los AngelesLos AngelesUSA

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