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 Et k activation in stably Etk-transfected epithelial Pa-4 cells resulted in a consistently increased transepithelial resistance (TER). After 24 h of hypo xic (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, r elative 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-acti vated cells displayed a redistribution of actin to an exclusively periphera l network, with a discrete band of beta -catenin also concentrated at the c ell periphery, and an altered occludin distribution profile. On the basis o f these findings, we propose that Etk may be a novel regulator of epithelia l junctions during physiological and pathophysiological conditions.