SASH1 Is a Scaffold Molecule in Endothelial TLR4 Signaling.
|Authors||Dauphinee SM, Clayton A, Hussainkhel A, Yang C, Park YJ, Fuller ME, Blonder J, Veenstra TD & Karsan A.|
|Abstract||Recognition of microbial products by TLRs is critical for mediating innate immune responses to invading pathogens. In this study, we identify a novel scaffold protein in TLR4 signaling called SAM and SH3 domain containing protein 1 (SASH1). Sash1 is expressed across all microvascular beds and functions as a scaffold molecule to independently bind TRAF6, TAK1, IκB kinase α, and IκB kinase β. This interaction fosters ubiquitination of TRAF6 and TAK1 and promotes LPS-induced NF-κB, JNK, and p38 activation, culminating in increased production of proinflammatory cytokines and increased LPS-induced endothelial migration. Our findings suggest that SASH1 acts to assemble a signaling complex downstream of TLR4 to activate early endothelial responses to receptor activation.|
|Journal Name and Citation||
J Immunol. 2013 Jul 15;191(2):892-901.
|Date of Publication||2013/07/15|