The nuclear factor of activated T cells (NF-AT) transcription factor family plays a pivotal role in T lymphocyte activation. NF-AT proteins regulate the T lymphocyte activation-dependent expression of several important cytokine genes, including IL-2, IL-3, IL-4, IL-5 and GM-CSF, as well as the expression of other immunologically important molecules such as CD40L and Fas. In concert, these gene products play a crucial role in regulating and coordinating the immune response. Understanding the mechanisms involved in the regulation of NF-AT will therefore provide important insights into the molecular mechanisms underlying the co-ordinate regulation of T lymphocyte activation genes and the initiation and regulation of the T lymphocyte immune response. NF-AT proteins appear to be regulated primarily by their subcellular localization. In resting T lymphocytes, NF-AT is located in the cytoplasm; however following antigen-receptor stimulation and the activation of calcineurin, NF-AT translocates from the cytoplasm to the nucleus, whereupon it can bind DNA and activate transcription.
In aim 1, NF-ATc binding proteins implicated in the regulation of NF-ATc activity will be isolated and characterized.
In aim 2, functionally important phosphorylation sites in NF-ATc will be identified and the role of these sites in the regulation of NF-ATc activity will be examined.
In aim 3, the kinases responsible for phosphorylating functionally important NF-ATc residues in vivo will be identified and characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29GM055292-02
Application #
2750131
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Neal, Joel W; Clipstone, Neil A (2003) A constitutively active NFATc1 mutant induces a transformed phenotype in 3T3-L1 fibroblasts. J Biol Chem 278:17246-54
Neal, Joel W; Clipstone, Neil A (2002) Calcineurin mediates the calcium-dependent inhibition of adipocyte differentiation in 3T3-L1 cells. J Biol Chem 277:49776-81