| First Author | Dauphinee SM | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 2 | Pages | 892-901 |
| PubMed ID | 23776175 | Mgi Jnum | J:205449 |
| Mgi Id | MGI:5544880 | Doi | 10.4049/jimmunol.1200583 |
| Citation | Dauphinee SM, et al. (2013) SASH1 is a scaffold molecule in endothelial TLR4 signaling. J Immunol 191(2):892-901 |
| abstractText | 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, IkappaB kinase alpha, and IkappaB kinase beta. This interaction fosters ubiquitination of TRAF6 and TAK1 and promotes LPS-induced NF-kappaB, 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. |
