Application Abstract): Local stimuli regulate the activity of Src-family tyrosine kinases (SFKs) present on the apical surface of epithelial cells. The SFK Yes is compartmentalized at the apical membrane by indirect interaction with the subapical scaffolding protein ERM phosphoprotein 50 (EBP50) that also associates with Cystic Fibrosis transmembrane regulator (CFTR) and ENaC. The proposed experiments will: 1) identify SFK's that regulate ion transport in the airway; 2) chracterize interactions that are involved in forming multiprotein complexes containing ENaC and SFK's; and 3) identify luminal stimuli that activate apical SFK's to modulate apical ion transport and determine how SFK's regulate the activities of ion channels. Together, the experiments will critically test the hypothesis that local regulation of apical ion transport in airway epithelia requires the formation of apical signaling complexes, and that one critical component of these complexes is a SFK.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063755-02
Application #
6351585
Study Section
Lung Biology and Pathology Study Section (LBPA)
Program Officer
Banks-Schlegel, Susan P
Project Start
2000-02-01
Project End
2005-01-31
Budget Start
2001-02-01
Budget End
2002-01-31
Support Year
2
Fiscal Year
2001
Total Cost
$301,842
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Gilmore, E S; Stutts, M J; Milgram, S L (2001) SRC family kinases mediate epithelial Na+ channel inhibition by endothelin. J Biol Chem 276:42610-7

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