Etk/Bmx activation modulates barrier function in epithelial cells.
Etk/Bmx is a member of the Tec family of cytoplasmic non-receptor tyrosine kinases known to express in epithelial cells. We demonstrate herein that Etk activation in stably Etk-transfected epithelial Pa-4 cells resulted in a consistently increased transepithelial resistance (TER). After 24 h of hypoxic (1% O(2)) exposure, the TER and equivalent active ion transport rate (I(eq)) were reduced to <5% of the normoxia control in Pa-4 cells, whereas both TER and I(eq) were maintained at comparable and 60% levels, respectively, relative to their normoxic controls in cells with Etk activation. Moreover, Pa-4 cells exhibited an abundant actin stress fiber network with a diffuse distribution of beta-catenin at the cell periphery. By contrast, Etk-activated cells displayed a redistribution of actin to an exclusively peripheral network, with a discrete band of beta-catenin also concentrated at the cell periphery, and an altered occludin distribution profile. On the basis of these findings, we propose that Etk may be a novel regulator of epithelial junctions during physiological and pathophysiological conditions.
Hamm-Alvarez
S F
SF
Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Chang
A
A
Wang
Y
Y
Jerdeva
G
G
Lin
H H
HH
Kim
K J
KJ
Ann
D K
DK
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002458:Cell Fractionation; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D003902:Detergents; D017097:Electric Impedance; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D062793:Occludin; D010306:Parotid Gland / Q000166:cytology; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D022502:Stress Fibers / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D015534:Trans-Activators; D051176:beta Catenin
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D003902:Detergents; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D013844:Thiazoles; D053778:Thiazolidines; D015534:Trans-Activators; D051176:beta Catenin; C492365:Bmx protein, rat; D011505:Protein-Tyrosine Kinases; C037067:latrunculin A