The proposed project involves developing a targeting construct that will generate tissue-specific expression of a constitutively active form of protein kinase A (PKA). Examination of the expression of this unregulated protein in embryonic stem cells (ES cells) compared to cells expressing either normal or decreased levels of PKA will allow us to determine the role of PKA in ES cell proliferation and differentiation into distinct cell fates. Contribution of these targeted ES cells to the germline of mice will permit expression of this protein in specific tissues under experimentally controlled conditions. Preliminarily, we plan to study the effect of this constitutively active PKA enzyme in the regulation of adiposity and weight regulation, processes that are known to involve PKA. We predict that mice expressing this constitutively active form of PKA in adipose tissue will exhibit a lean phenotype, contributing to our understanding of body weight regulation and suggesting possible treatments for obesity in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK010005-02
Application #
6362971
Study Section
Biological Sciences 2 (BIOL)
Program Officer
Hyde, James F
Project Start
2001-03-01
Project End
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
2
Fiscal Year
2001
Total Cost
$41,936
Indirect Cost
Name
University of Washington
Department
Pharmacology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Willis, Brandon S; Niswender, Colleen M; Su, Thomas et al. (2011) Cell-type specific expression of a dominant negative PKA mutation in mice. PLoS One 6:e18772
Niswender, Colleen M; Ishihara, R Wesley; Judge, Luke M et al. (2002) Protein engineering of protein kinase A catalytic subunits results in the acquisition of novel inhibitor sensitivity. J Biol Chem 277:28916-22