Signal transduction to nucleus by phosphatidylinositol 3-kinase

为了了解磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI 3 K）的信号转导机制，我们研究了PI 3 K结合蛋白Swap-70的作用。我们的研究表明，Swap-70移动到细胞膜皱褶后，与生长因子的刺激，这种蛋白质是一个鸟嘌呤核苷酸交换因子（GEE）的Rac。该GEF活性被拒绝用于通过PI 3 K从生长因子受体向Rac的信号传导。与野生型小鼠相比，Swap-70缺陷小鼠的肾细胞培养物在EGF刺激后表现出受损的膜皱褶。Swap-70含有DH结构域和PH结构域，DH结构域表现出GEF活性，PH结构域负责PIP 3结合。PH结构域与DH结构域结合以抑制GEF活性。这种与PIP_3的结合被消除，表明PIP_3从PH结构域的抑制作用中释放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.