TY - JOUR
T1 - Coregulation of multiple signaling mechanisms in pp60v-Src-Induced Closure of Cx43 Gap Junction Channels
AU - Mitra, Siddhartha S.
AU - Xu, Ji
AU - Nicholson, Bruce J.
PY - 2012/8
Y1 - 2012/8
N2 - 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 phos-phorylation 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.
AB - 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 phos-phorylation 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.
KW - Cx43
KW - Erk1/2
KW - Gap junction
KW - Signal transduction
KW - V-Src
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U2 - 10.1007/s00232-012-9500-0
DO - 10.1007/s00232-012-9500-0
M3 - Article
C2 - 22965738
AN - SCOPUS:84866732613
VL - 245
SP - 495
EP - 506
JO - Journal of Membrane Biology
JF - Journal of Membrane Biology
SN - 0022-2631
IS - 8
ER -