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Association of Connexin43 with a Receptor Protein Tyrosine Phosphatase

机译：连接蛋白43与受体蛋白酪氨酸磷酸酶的关联。

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摘要

Connexin-43(Cx43)-based gap junctional communication is transiently inhibited by certain G protein-coupled receptor agonists, including lysophosphatidic acid, endothelin and thrombin. Our previous studies have implicated the c-Src protein tyrosine kinase in mediating closure of Cx43 based gap junctions. Pervanadate, an inhibitor of protein tyrosine phosphatases, mimics activated Src in inhibiting Cx43 gap junctional communication, apparently by promoting tyrosine phosphorylation of the Cx43 C-terminal tail. However, the identity of the protein tyrosine phosphatase(s) that may normally prevent Src-induced gap junction closure is unknown. Receptor-like protein tyrosine phosphatases that mediate homotypic cell-cell interaction are attractive candidates. Here we show that receptor protein tyrosine phosphatase μ(RPTPμ) interacts with Cx43 in diverse cell systems. We find that the first catalytic domain of RPTPμ binds to Cx43. Our results support a model in which RPTPμ, or a closely related protein tyrosine phosphatase, interacts with the regulatory C-terminal tail of Cx43 to prevent Src-mediated closure of Cx43 gap junctional channels.
机译：基于连接蛋白43（Cx43）的间隙连接通讯被某些G蛋白偶联受体激动剂（包括溶血磷脂酸，内皮素和凝血酶）暂时抑制。我们以前的研究已暗示c-Src蛋白酪氨酸激酶介导基于Cx43的间隙连接的闭合。过氧钒酸盐，一种蛋白质酪氨酸磷酸酶的抑制剂，显然是通过促进Cx43 C末端尾部的酪氨酸磷酸化来模拟激活的Src抑制Cx43间隙连接通讯。然而，通常可以阻止Src诱导的间隙连接关闭的蛋白酪氨酸磷酸酶的身份尚不清楚。介导同型细胞间相互作用的受体样蛋白酪氨酸磷酸酶是有吸引力的候选物。在这里，我们显示了受体蛋白酪氨酸磷酸酶μ（RPTPμ）在各种细胞系统中与Cx43相互作用。我们发现，RPTPμ的第一个催化域与Cx43结合。我们的结果支持一个模型，其中RPTPμ或紧密相关的蛋白酪氨酸磷酸酶与Cx43的C末端调节尾相互作用，以防止Src介导的Cx43间隙连接通道的关闭。

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