Recent evidence has shown that many of the cell surface receptors that initiate pathways leading to NF-kB activation show a dualistic behavior, with outputs that lead either to inflammatory responses or death. The nearly ubiquitous expression of receptors in the TNF receptor superfamily and the increasing evidence that many cell types outside the immune system are affected by TNF and related cytokines in ways that are substantially broader than previously supposed argue for a closer examination of the cell specific features of NF-kB activation. In this application we propose to undertake a search for new cDNAs that have the power to induce NF-kB activity when overexpressed in a reporter cell line, and to explore the physiological partners for those proteins by two-hybrid, pulldown and epistasis experiments in culture. In addition, we propose to gain insight into the natural physiology of NF-kB activation by studying the contexts that lead to reporter gene activation in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI046731-03
Application #
6511195
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Mallia, Conrad M
Project Start
2000-03-01
Project End
2005-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
3
Fiscal Year
2002
Total Cost
$356,319
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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Xavier, Ramnik; Rabizadeh, Shahrooz; Ishiguro, Kazuhiro et al. (2004) Discs large (Dlg1) complexes in lymphocyte activation. J Cell Biol 166:173-8
Yang, Yi; Seed, Brian (2003) Site-specific gene targeting in mouse embryonic stem cells with intact bacterial artificial chromosomes. Nat Biotechnol 21:447-51
Lichtenthaler, Stefan F; Dominguez, Diana-Ines; Westmeyer, Gil G et al. (2003) The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1. J Biol Chem 278:48713-9