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，我们探讨了PIP_3结合蛋白的作用，特别是对SWAP-70蛋白的作用。我们的研究表明，SWAP-70在生长因子刺激后移动到膜皱纹上，该蛋白是RAC的鸟嘌呤核苷酸交换因子(GEE)。这种全球环境基金活性被拒绝，因为生长因子受体通过PI3K向RAC发出信号。与野生型小鼠相比，SWAP-70基因缺陷小鼠肾细胞培养物在EGF刺激后出现了膜褶皱的损伤。SWAP-70含有一个具有全球环境基金活性的水解区和一个负责PIP3结合的PH域。PH结构域与DH结构域结合以抑制全球环境基金的活性。这种与PIP_3的结合被取消，这表明PIP_3释放了PH结构域的抑制作用。

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.