title: Regulation of connexin43 function by activated tyrosine protein kinases.
abstract: Gap junctions are specialized membrane structures that are involved in the normal functioning of numerous mammalian tissues and implicated in several human disease processes. This mini-review focuses on the regulation of gap junctions through phosphorylation of connexin43 induced by the v-Src or epidermal growth factor receptor tyrosine kinases. These tyrosine kinases markedly disrupt gap junctional communication in mammalian cells. here, we describe work correlating the alteration of connexin43 function with the ability of the v-Src tyrosine kinase to phosphorylate connexin43 directly on two distinct tyrosine sites in mammalian cells (Y247 and Y265). We also present evidence that proline-rich regions and phosphotyrosine sites of connexin43 may mediate interactions with the SH3 and SH2 domains of v-Src. In contrast to v-Src, the activated epidermal growth factor receptor acts indirectly through activated MAP kinase which may stimulate phosphorylation of connexin43 exclusively on serine. This phosphorylation event is complex because MAP kinase phosphorylates three serine sites in connexin43 (S255, S279, and S282). These findings suggest novel interactions between connexin43, the v-Src tyrosine kinase, and activated MAP kinase that set the stage for future investigations into the regulation of gap junctions by protein phosphorylation.
authors.affiliation: Cancer Research Center, University of Hawaii at Manoa, Honolulu, Hawaii.
authors.forename: A F
authors.initials: AF
authors.lastname: Lau
authors.forename: W E
authors.initials: WE
authors.lastname: Kurata
authors.forename: M Y
authors.initials: MY
authors.lastname: Kanemitsu
authors.forename: L W
authors.initials: LW
authors.lastname: Loo
authors.forename: B J
authors.initials: BJ
authors.lastname: Warn-Cramer
authors.forename: W
authors.initials: W
authors.lastname: Eckhart
authors.forename: P D
authors.initials: PD
authors.lastname: Lampe
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D018031:Connexin 43; D011505:Protein-Tyrosine Kinases