Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063755-04
Application #
6629039
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
2003-02-01
Budget End
2004-01-31
Support Year
4
Fiscal Year
2003
Total Cost
$339,837
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Morin-Kensicki, Elizabeth M; Boone, Brian N; Howell, Michael et al. (2006) Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Mol Cell Biol 26:77-87
Hodson, Caleb A; Ambrogi, Ilana G; Scott, Robert O et al. (2006) Polarized apical sorting of guanylyl cyclase C is specified by a cytosolic signal. Traffic 7:456-64
Thelin, William R; Hodson, Caleb A; Milgram, Sharon L (2005) Beyond the brush border: NHERF4 blazes new NHERF turf. J Physiol 567:13-9
Howell, Michael; Borchers, Christoph; Milgram, Sharon L (2004) Heterogeneous nuclear ribonuclear protein U associates with YAP and regulates its co-activation of Bax transcription. J Biol Chem 279:26300-6
Kast, Juergen; Parker, Carol E; van der Drift, Koen et al. (2003) Matrix-assisted laser desorption/ionization directed nano-electrospray ionization tandem mass spectrometric analysis for protein identification. Rapid Commun Mass Spectrom 17:1825-34
Smith, Perry M; Cowan, Ann; Milgram, Sharon L et al. (2003) Tissue-specific regulation by estrogen of ezrin and ezrin/radixin/moesin-binding protein 50. Endocrine 22:119-26
Scott, Robert O; Thelin, William R; Milgram, Sharon L (2002) A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor. J Biol Chem 277:22934-41
Lee, Shaun W; Bonnah, Robert A; Higashi, Dustin L et al. (2002) CD46 is phosphorylated at tyrosine 354 upon infection of epithelial cells by Neisseria gonorrhoeae. J Cell Biol 156:951-7
Brdickova, N; Brdicka, T; Andera, L et al. (2001) Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton. FEBS Lett 507:133-6
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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