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. |
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| 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 |
| Publication Link | http://www.jimmunol.org/content/191/2/892.long |