Pharmaceutical Sciences Faculty Publications

Title

SASH1 Is a Scaffold Molecule in Endothelial TLR4 Signaling

Document Type

Article

Publication Date

7-15-2013

Journal Title

Journal of Immunology

ISSN

1550-6606

Volume

191

Issue

2

First Page

892

Last Page

901

DOI

10.4049/jimmunol.1200583

PubMed ID

23776175

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.

Keywords

Endothelial cells, enzyme activation, immunity, innate, lipopolysaccharides, RNA interference, signal transduction, tumor suppressor proteins

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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