This is a proposal to analyze rho-dependent signaling pathways. The main feature of this proposal involves the use of a novel delivery system utilizing Sindbis-virus based vectors. This will permit co-expression of several C3-resistant rho isoforms (and modifications thereof) in conjunction with the specific inhibitor of rho, the C3 exoenzyme, which will inactivate endogenous rho activity. It is argued that this is a more efficient mechanism of delivery than other procedures. Using this approach the investigator will determine if there are any differences in function of rho A, B and C. Mutational analysis will be used to identify potential regions in the C-terminus controlling subcellular localization and regions within the effector domain required for rho dependent cellular functions. Finally, the mutants will be used to identify potential downstream effectors or signaling partners of rho. This will include attempts to identify and characterize binding partners.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054572-03
Application #
2750097
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1996-08-01
Project End
2000-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904