Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity.
Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity.
复制标题
Galpha(12) 和 Galpha(13) 与 Ser/Thr 蛋白磷酸酶 5 型相互作用并刺激其磷酸酶活性。
作者：
Y. Yamaguchi;H. Katoh;K. Mori;M. Negishi
异源三聚体G蛋白的G（12）家族的G α亚基，由G α（12）和G α（13）定义，参与许多信号传导途径和多种细胞功能。为了阐明Ga（12）的细胞功能下游效应物，我们对大鼠脑cDNA文库进行了酵母双杂交筛选，并发现Ser/Thr蛋白磷酸酶5型（PP 5）是Ga（12）和Ga（13）的新效应物。PP 5是一种新发现的磷酸酶，由C端催化结构域和N端调节性三肽重复（TPR）结构域组成[2]。花生四烯酸最近被证明可以通过与其TPR结构域结合来激活PP 5磷酸酶活性，然而PP 5磷酸酶活性的精确调节机制尚未完全确定。在这项研究中，我们发现活性形式的Ga（12）和Ga（13）通过其TPR结构域与PP 5特异性相互作用，并激活其磷酸酶活性约2.5倍。活性形式的Ga（12）和Ga（13）也使花生四烯酸刺激的PP 5磷酸酶活性增强约2.5倍。此外，我们证明了活性形式的G α（12）易位PP 5的细胞周边和共定位与PP 5。这些结果提出了一个新的G（12）家族G蛋白信号通路。
The Galpha subunits of the G(12) family of heterotrimeric G proteins, defined by Galpha(12) and Galpha(13), are involved in many signaling pathways and diverse cellular functions. In an attempt to elucidate downstream effectors of Galpha(12) for cellular functions, we have performed a yeast two-hybrid screening of a rat brain cDNA library and revealed that Ser/Thr protein phosphatase type 5 (PP5) is a novel effector of Galpha(12) and Galpha(13). PP5 is a newly identified phosphatase and consists of a C-terminal catalytic domain and an N-terminal regulatory tetratricopeptide repeat (TPR) domain [2]. Arachidonic acid was recently shown to activate PP5 phosphatase activity by binding to its TPR domain, however the precise regulatory mechanism of PP5 phosphatase activity is not fully determined. In this study, we show that active forms of Galpha(12) and Galpha(13) specifically interact with PP5 through its TPR domain and activate its phosphatase activity about 2.5-fold. Active forms of Galpha(12) and Galpha(13) also enhance the arachidonic acid-stimulated PP5 phosphatase activity about 2.5-fold. Moreover, we demonstrate that the active form of Galpha(12) translocates PP5 to the cell periphery and colocalizes with PP5. These results propose a new signaling pathway of G(12) family G proteins.