Department of Biotechnology, University of Kashmir, India.
Exp Cell Res. 2012 Dec 10;318(20):2559-66. doi: 10.1016/j.yexcr.2012.08.004. Epub 2012 Aug 30.
Connexin 43 (Cx43) is a phosphoprotein expressed in a wide variety of cells. Cx43 and adenosine-triphosphate-sensitive K(+)channels [K(+)(ATP)] are part of same signaling pathway that regulates cell survival during stress and ischemia preconditioning. Molecular mechanism for their coordinated role in ischemia/hypoxia preconditioning is not well known. Using pull down, co-immunoprecipitation assays and co-localization studies we provide evidence, for the first time that Kir6.1, a K(+)(ATP) channel protein component, can interact with Cx43. Further we show that the interaction was phospho-specific such that Cx43 phosphorylated at serine 262 (S262) interacted with Kir6.1 in preference to the unphosphorylated form of Cx43. Introduction of phospho-deficient mutation at serine 262 (S262A) in Cx43 completely abolished the interaction. Our data provide an interesting lead about a possible partnership between Cx43 and Kir6.1, which will help in better understanding their role in ischemia/hypoxia preconditioning.
间隙连接蛋白 43（Cx43）是一种在多种细胞中表达的磷酸化蛋白。Cx43 和三磷酸腺苷敏感性钾（K+）通道（K+（ATP））是同一信号通路的一部分，该通路调节应激和缺血预处理期间的细胞存活。它们在缺血/缺氧预处理中协调作用的分子机制尚不清楚。通过下拉、共免疫沉淀测定和共定位研究，我们首次提供了证据，表明 Kir6.1（一种 K+（ATP）通道蛋白成分）可以与 Cx43 相互作用。此外，我们还表明，这种相互作用是磷酸化特异性的，即 Cx43 磷酸化的丝氨酸 262（S262）与 Kir6.1 相互作用，而不是与 Cx43 的未磷酸化形式相互作用。在 Cx43 中引入丝氨酸 262（S262A）的磷酸缺陷突变完全消除了相互作用。我们的数据提供了一个有趣的线索，即 Cx43 和 Kir6.1 之间可能存在伙伴关系，这将有助于更好地理解它们在缺血/缺氧预处理中的作用。
