@article {64943,
	title = {Time-variant SRC kinase activation determines endothelial permeability response.},
	journal = {Cell Chemical Biology},
	volume = {26},
	year = {2019},
	month = {2019 Aug 15},
	pages = {1081-94},
	abstract = {<p>In the current model of endothelial barrier regulation, the tyrosine kinase SRC is purported to induce disassembly of endothelial adherens junctions (AJs) via\&nbsp;phosphorylation of VE cadherin, and thereby increase\&nbsp;junctional permeability. Here, using a chemical biology approach to temporally control SRC activation,\&nbsp;we show that SRC exerts distinct time-variant effects on the endothelial barrier. We discovered that the immediate effect of SRC activation was to transiently enhance endothelial barrier function as the result of accumulation of VE cadherin at AJs and formation of morphologically distinct reticular AJs. Endothelial barrier enhancement via SRC required phosphorylation of VE cadherin at Y731. In contrast, prolonged SRC activation induced VE cadherin phosphorylation at Y685, resulting in increased endothelial permeability. Thus, time-variant SRC activation differentially phosphorylates VE cadherin and shapes AJs to fine-tune endothelial barrier function. Our work demonstrates important advantages of synthetic biology tools in dissecting complex signaling systems.</p>
},
	issn = {2451-9448},
	doi = {10.1016/j.chembiol.2019.04.007},
	author = {Klomp, Jennifer E and Shaaya, Mark and Matsche, Jacob and Rebiai, Rima and Aaron, Jesse S and Collins, Kerrie B and Huyot, Vincent and Gonzalez, Annette M and Muller, William A and Chew, Teng-Leong and Malik, Asrar B and Karginov, Andrei V}
}
