The Ah-receptor (AHR) is a ligand-activated transcription factor found in nearly all vertebrate species examined to date. The AHR mediates an adaptive response to planar aromatic hydrocarbon ligands by up-regulating a battery of genes that ultimately metabolize the ligand molecule. Recently, examinations of AHR knockout mice have revealed that AHR is required for normal vascular development. This second observation suggests that AHR signaling is triggered during development, and that an endogenous signal may activate the AHR. The goal of this project is to identify genes that can activate or inhibit AHR signaling in vivo. By identifying cellular factors that regulate ARR signaling, we may gain insight into the role of this protein in development. We propose that this information will provide insight as to the identity of an endogenous AHR ligand or whether AHR is capable of being activated in the absence of ligand during development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32ES011070-01
Application #
6340202
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Shreffler, Carol K
Project Start
2001-04-01
Project End
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Bittinger, Mark A; Nguyen, Linh P; Bradfield, Christopher A (2003) Aspartate aminotransferase generates proagonists of the aryl hydrocarbon receptor. Mol Pharmacol 64:550-6