The long term goal of this project is to understand how Src can induce the formation of podosomes leading to an invasive phenotype. Many human cancers have elevated Src kinase activity, and tumor progression, especially metastatic tumors, correlates with this increase in activity. Increased Src activity constitutively stimulates many downstream signaling pathways leading to the formation of invasive structures termed podosomes. Podosomes are sites of actin polymerization, cell attachment and protease secretion. Many proteins associated with these processes are direct Src substrates. We hope to gain insight into what proteins and signaling pathways are essential for podosome formation and cellular invasion. To do this, we are going to utilize RNAi technology to knockout the integrin-F-actin linker protein and Src substrate vinculin. We can then test how Src phosphorylation of vinculin effects its overall function in vivo. Second, we are going to look at the role of ERK5 in podosome formation and invasion. Preliminary data from our lab indicate that ERK5 activity is required for podosome formation. Using ERK5 -/- cells we will express an activated form of Src and determine its capacity to induce podosome formation. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31CA126472-01
Application #
7230750
Study Section
Special Emphasis Panel (ZRG1-EMNR-E (29))
Program Officer
Bini, Alessandra M
Project Start
2007-03-14
Project End
2009-03-13
Budget Start
2007-03-14
Budget End
2008-03-13
Support Year
1
Fiscal Year
2006
Total Cost
$30,043
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Schramp, Mark; Ying, Olivia; Kim, Tai Young et al. (2008) ERK5 promotes Src-induced podosome formation by limiting Rho activation. J Cell Biol 181:1195-210