Signal transduction to nucleus by phosphatidylinositol 3-kinase

为了了解磷脂酰肌醇3-激酶（PI3K）的信号转导，我们探索了pip3结合蛋白，特别是Swap-70蛋白的作用。Swap-70被认为是一种无处不在的分布，这表明了它的其他功能。我们的研究表明Swap-70在生长因子刺激后移动到膜褶边，该蛋白是Rac的鸟嘌呤核苷酸交换因子（GEE）。这种GEF活性在生长因子受体通过PI3K向Rac传递信号时被拒绝。与野生型小鼠相比，Swap-70缺陷小鼠的肾细胞培养物在EGF刺激后显示出膜褶皱受损。Swap-70包含一个具有GEF活性的DH结构域和一个负责PIP3结合的PH结构域。PH结构域结合DH结构域抑制GEF活性。这种与PIP_3的结合被取消，表明PIP_3从PH结构域的抑制作用中释放了DH结构域。

We have explored the roles of PIP_3 binding proteins, especially on Swap-70 protein, in order to understand the signal transduction of phosphatidylinositol 3-kinase (PI3K).Swap-70 has been identified as a ubiquitous distribution suggested its other functions. Our study revealed that Swap-70 moved to the membrane ruffles after stimulation with growth factors and that this protein was a guanine nucleotide exchange factor (GEE) for Rac. This GEF activity was refused for signaling from growth factor receptors to Rac via PI3K. Kidney cell cultures established from Swap-70 deficient mice showed impaired membrane ruffling after EGF stimulation compared with those for wild type mice.Swap-70 contains a DH domain, which exhibits the GEF activity, and a PH domain responsible for PIP3 binding. The PH domain binds to the DH domain to inhibit the GEF activity. This binding was abolished to PIP_3, suggestion that PIP_3 releases the DH domain from the inhibitory effect of the PH domain.