Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR-induced disruption
Cara C. Rada, Hilda Mejia-Pena, Neil Grimsey, Isabel Canto Cordova, Joshua Olson, Jacob M. Wozniak, David J. Gonzalez, Victor Nizet, JoAnn Trejo
Abstract
phosphorylation. Thrombin-stimulated p38-MK2-MK3 signaling induced HSP27 oligomer disassembly. However, a phosphorylation-deficient mutant of HSP27 exhibited defective oligomer disassembly and altered the dynamics of barrier recovery after thrombin stimulation. Moreover, blocking HSP27 oligomer reassembly with the small-molecule inhibitor J2 enhanced endothelial barrier permeability in vitro and vascular leakage in vivo in response to PAR1 activation. These studies reveal the distinct regulation of HSP27 phosphorylation and function induced by the GPCR-stimulated p38-MK2-MK3 signaling axis that controls the dynamics of endothelial barrier recovery in vitro and vascular leakage in vivo.