Integrins are intimately involved in a diversity of biological processes and are proven therapeutic targets for several diseases. Talin binding to integrin has been demonstrated to be the common final step in integrin activation, but the signaling mechanisms by which regulates integrin activation are unknown. It has been reported that talin undergo rapid phosphorylation accompanying focal adhesion disassembly when fibroblasts are exposed to stimuli, but the roles of talin phosphorylation are unclear. This proposal aims to identify the talin phosphorylation sites and the responsible protein kinases in vitro and in vivo, to examine the role of talin phosphorylation in cell migration, focal adhesion dynamics, and integrin activation, and to dissect the molecular mechanism. The results from the proposed experiments will provide valuable insights into the molecular mechanisms for regulating integrin activation. The identified protein kinases responsible for talin phosphorylation will be potential therapeutic targets.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL083215-02
Application #
7105443
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Meadows, Tawanna
Project Start
2005-07-14
Project End
2007-03-13
Budget Start
2006-07-14
Budget End
2007-03-13
Support Year
2
Fiscal Year
2006
Total Cost
$31,381
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Huang, Cai; Jacobson, Ken (2010) Detection of protein-protein interactions using nonimmune IgG and BirA-mediated biotinylation. Biotechniques 49:881-6
Huang, Cai; Rajfur, Zenon; Yousefi, Nima et al. (2009) Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration. Nat Cell Biol 11:624-30