SASH1 Is a Scaffold Molecule in Endothelial TLR4 Signaling
Journal of Immunology
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.
Endothelial cells, enzyme activation, immunity, innate, lipopolysaccharides, RNA interference, signal transduction, tumor suppressor proteins
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.