Pharmaceutical Sciences Faculty Publications
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
Recommended Citation
Dauphinee, Shauna M.; Clayton, Ashley; Hussainkhel, Angela; Yang, Cindy; Park, Yoo-Jin; Fuller, Megan E.; Blonder, Josip; Veenstra, Timothy D.; and Karsan, Aly, "SASH1 Is a Scaffold Molecule in Endothelial TLR4 Signaling" (2013). Pharmaceutical Sciences Faculty Publications. 198.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/198
