PI 3-KINASE AND VSRC TRANSFORMATION

这项提案的总体目标是确定 磷脂酰肌醇3-K在恶性转化中的作用 按v-Src。PI3-K及其下游信号通路的激活可能 与Ras-MAP激酶途径协同介导v-Src 转型。因此，v-Src对PI 3-K的激活作用将是 在RAS激活被阻断的细胞中进行监测。这一点的作用 PI3-K在转化过程中的激活将通过确定 抑制PI3-K对v-Src转化的影响以确定哪些是 已知的PI3-K效应子中的一个对于v-Src的转化是必需的， Rac、Akt和p70S6K的激活将在细胞中进行监测 表达v-Src和抑制转化的程度将是 已确定这三条路径中的每一条都被阻塞的时间。最后， V-Src激活PI3-K的机制将通过 V-Src和V-Src直接激活的各自贡献 通过对接中间件激活。对…的全面了解 V-Src恶性转化过程中的信号转导途径 是理解细胞生长变化的基础 对癌症负有责任。

The overall objective of this proposal is to determine the role that phosphatidylinositide 3-kinase (PI3-K) plays in malignant transformation by v-Src. Activation of PI3-K and its downstream signaling pathways may cooperate with the Ras-MAP kinase pathway in mediating v-Src transformation. Therefore, the activation of PI 3-K by v-Src will be monitored in cells in which Ras activation is blocked. The role of this PI3-K activation in transformation will be examined by determining the effect of inhibiting PI3-K on v-Src transformation. To identify which of the known PI3-K effectors is necessary for transformation by v-Src, the activation of Rac, Akt, and p70S6k will be monitored in cells expressing v-Src and the extent of inhibition of transformation will be determined when each of these three pathways is blocked. Finally, the mechanism by which v-Src activates PI3-K will be studied by examining the respective contributions of direct activation by v-Src and activation through a docking intermediate. A complete understanding of the signaling pathways involved in malignant transformation by v-Src may serve as a basis for understanding the alterations in cell growth responsible for cancer.