PI 3-KINASE AND VSRC TRANSFORMATION

PI 3-激酶和 VSRC 转化

• 批准号: 6173663
• 负责人: BRIAN L WEBB
• 金额: $ 1.74万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6173663
• 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.

该提案的总体目标是确定以下角色： 磷脂酰肌醇 3-激酶 (PI3-K) 在恶性转化中发挥作用 由 v-Src 提供。 PI3-K 及其下游信号通路的激活可能 与 Ras-MAP 激酶通路合作介导 v-Src 转变。 因此，v-Src 对 PI 3-K 的激活将是 在 Ras 激活被阻断的细胞中进行监测。 这个的作用 转化中的 PI3-K 激活将通过确定 抑制 PI3-K 对 v-Src 转化的影响。 以确定哪个 已知的 PI3-K 效应子对于 v-Src 的转化是必需的， 将监测细胞中 Rac、Akt 和 p70S6k 的激活 表达 v-Src 和转化抑制程度为 确定这三种途径中的每一种何时被阻断。 最后， v-Src 激活 PI3-K 的机制将通过检查来研究 v-Src 直接激活的各自贡献和 通过对接中间体激活。 完整的了解 v-Src参与恶性转化的信号通路可能 作为了解细胞生长变化的基础 对癌症负责。

项目成果

v-Src generates a p53-independent apoptotic signal.

v-Src 产生独立于 p53 的细胞凋亡信号。

• DOI: 10.1128/mcb.20.24.9271-9280.2000
• 发表时间: 2000
• 期刊: Molecular and cellular biology
• 影响因子: 5.3
• 作者: Webb,BL;Jimenez,E;Martin,GS
• 通讯作者: Martin,GS