1. Coregulation of multiple signaling mechanisms in pp60v-Src-induced closure of Cx43 gap junction channels.
- Author
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Mitra SS, Xu J, Nicholson BJ, Mitra, Siddhartha S, Xu, Ji, and Nicholson, Bruce J
- 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. [ABSTRACT FROM AUTHOR]
- Published
- 2012