title: PI3K/Akt signaling is involved in the disruption of gap junctional communication caused by v-Src and TNF-α.
abstract: Gap junctional communication, which is mediated by the connexin protein family, is essential for the maintenance of normal tissue function and homeostasis. Loss of intercellular communication results in a failure to coordinately regulate cellular functions, and it can facilitate tumorigenesis. Expression of oncogenes and stimulation with cytokines has been shown to suppress intercellular communication; however, the exact mechanism by which intercellular communication is disrupted by these factors remains uncertain. In this report, we show that Akt is essential for the disruption of gap junctional communication in v-Src-transformed cells. In addition, inhibition of Akt restores gap junctional communication after it is suppressed by TNF-α signaling. Furthermore, we demonstrate that the expression of a constitutively active form of Akt1, but not of Akt2 or Akt3, is sufficient to suppress gap junctional communication. Our results clearly define Akt1 as one of the critical regulators of gap junctional communication.
authors: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Satoko
authors: S
authors: Ito
authors: Toshinori
authors: T
authors: Hyodo
authors: Hitoki
authors: H
authors: Hasegawa
authors: Hong
authors: H
authors: Yuan
authors: Michinari
authors: M
authors: Hamaguchi
authors: Takeshi
authors: T
authors: Senga
mesh_terms: D000818:Animals; D002450:Cell Communication; D002461:Cell Line, Transformed; D017629:Gap Junctions / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D015688:Oncogene Protein pp60(v-src); D051057:Proto-Oncogene Proteins c-akt