Signal transduction to nucleus by phosphatidylinositol 3-kinase

磷脂酰肌醇 3-激酶将信号转导至细胞核

• 批准号: 12460039
• 负责人: FUKUI Yasuhisa
• 金额: $ 9.02万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12460039/
• 关键词: phosphoinositides; PH domain; GEF; PIP_3; Rac; Ruffling; signal transduction; growth factors; ホスファチジルイノシトール3キナーゼ; 核移行; グアニンヌクレオチド交換因子; GTPase促進活性因子; ラッフル膜; Gタンパク質; 核外輸送

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.

我们探索了 PIP_3 结合蛋白的作用，特别是 Swap-70 蛋白的作用，以了解磷脂酰肌醇 3-激酶 (PI3K) 的信号转导。Swap-70 已被确定为普遍存在的分布，表明了其其他功能。我们的研究表明，在生长因子刺激后，Swap-70 移动到膜皱褶处，并且该蛋白质是 Rac 的鸟嘌呤核苷酸交换因子 (GEE)。由于生长因子受体通过 PI3K 向 Rac 发出信号，因此 GEF 活性被拒绝。与野生型小鼠相比，Swap-70 缺陷小鼠建立的肾细胞培养物在 EGF 刺激后表现出受损的膜皱褶。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 结构域与 DH 结构域结合以抑制 GEF 活性。 PIP_3 取消了这种结合，表明 PIP_3 将 DH 结构域从 PH 结构域的抑制作用中释放出来。