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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA077915-03
Application #
6173663
Study Section
Biological Sciences 2 (BIOL)
Program Officer
Lohrey, Nancy
Project Start
2000-05-01
Project End
Budget Start
2000-05-01
Budget End
2000-10-15
Support Year
3
Fiscal Year
2000
Total Cost
$17,362
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Webb, B L; Jimenez, E; Martin, G S (2000) v-Src generates a p53-independent apoptotic signal. Mol Cell Biol 20:9271-80