title: Coregulation of multiple signaling mechanisms in pp60v-Src-induced closure of Cx43 gap junction channels.
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.
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
authors.forename: Siddhartha S
authors.initials: SS
authors.lastname: Mitra
authors.forename: Ji
authors.initials: J
authors.lastname: Xu
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D018031:Connexin 43; D015688:Oncogene Protein pp60(v-src)