PI 3-KINASE AND VSRC TRANSFORMATION

PI 3-激酶和 VSRC 转化

• 批准号: 2640846
• 负责人: BRIAN L WEBB
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-10-19 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2640846
• 关键词: biological signal transduction; chick embryo; neoplastic transformation; oncogenes; phosphatidylinositol 3 kinase

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.

本建议的总体目标是确定 磷脂酰肌醇3-激酶（PI 3-K）在恶性转化中的作用 通过v-Src。 PI 3-K及其下游信号通路的激活可能 与Ras-MAP激酶通路协同介导v-Src 转型 因此，v-Src对PI 3-K的活化将是 在Ras激活被阻断的细胞中监测。 中的作用 将通过测定转化中的PI 3-K活化来检查转化中的PI 3-K活化。 抑制PI 3-K对v-Src转化的影响。 来识别哪些 已知的PI 3-K效应子的一部分是v-Src转化所必需的， 将在细胞中监测Rac、Akt和p70 S6 k活化 表达v-Src，抑制转化的程度将是 确定这三种途径中的每一种何时被阻断。 最后 将通过检查研究v-Src激活PI 3-K的机制 v-Src直接激活的各自贡献， 通过对接中间体激活。 完全理解 参与v-Src恶性转化的信号通路可能 作为理解细胞生长变化的基础 负责癌症。