Regulation of lung endothelial permeability by NEK kinases

Abstract

Dysregulation of lung endothelial barrier function may lead to lethal outcomes, as demonstrated in the case of the acute respiratory distress syndrome (ARDS). p53 participates in the regulation of the lung endothelial barrier, and it has been associated both in vivo and in vitro with protective effects against the LPS-induced hyperpermeability. Family members of the never in mitosis A-related kinases (NEKs) are crucial mediators of fundamental cellular processes, including mitosis, and have been shown to posttranslationally modify p53. Since such modifications affect p53 stability and activity, it is highly probable that NEK kinases are also regulators of lung endothelial permeability. Thus, they may serve as possible therapeutic targets for treatment of pathologies associated with endothelial barrier dysfunction.