The Shc gene encodes three proteins that are widely expressed and that contribute to signal transduction by a wide variety of protein-tyrosine kinases. Both cytoplasmic and receptor protein-tyrosine kinases can become oncogenically activated and Shc is highly tyrosine-phosphorylated in cells that express oncogenically activated protein-tyrosine kinases. Shc proteins lack catalytic activity and are thought to function as a scaffold for protein-protein interactions. Two phosphotyrosine-binding modules and several tyrosine phosphorylation sites enable Shc to mediate several protein-protein interactions at the same time. Shc becomes tyrosine phosphorylated upon association with activated growth factor receptors. Tyrosine phosphorylated Shc associates with the Grb2-Sos complex and is thought to play a role in Ras activation. However, Shc's precise contribution to Ras activation remains poorly understood. It also remains unclear whether Shc performs functions independent of Ras. Their long-term goal is to understand Shc's function during normal and malignant signal transduction. To reach that goal, they propose to characterize the signaling abilities of a collection of Shc mutants in Shc-deficient cells. In addition, they will determine the differences in signaling between Shc and Grb2 following growth factor receptor activation and they propose to purify a Shc-binding protein from Src-transformed fibroblasts.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA078629-05
Application #
6513304
Study Section
Pathology B Study Section (PTHB)
Program Officer
Blair, Donald G
Project Start
1998-07-01
Project End
2003-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
5
Fiscal Year
2002
Total Cost
$128,408
Indirect Cost
Name
University of California San Diego
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093