دورية أكاديمية
SASH1 is a scaffold molecule in endothelial TLR4 signaling.
| العنوان: | SASH1 is a scaffold molecule in endothelial TLR4 signaling. |
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| المؤلفون: | Dauphinee SM; Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada., Clayton A, Hussainkhel A, Yang C, Park YJ, Fuller ME, Blonder J, Veenstra TD, Karsan A |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2013 Jul 15; Vol. 191 (2), pp. 892-901. Date of Electronic Publication: 2013 Jun 17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Endothelial Cells/*metabolism , TNF Receptor-Associated Factor 6/*metabolism , Toll-Like Receptor 4/*metabolism , Tumor Suppressor Proteins/*metabolism, Animals ; Cell Movement ; Enzyme Activation ; I-kappa B Kinase/metabolism ; Immunity, Innate ; JNK Mitogen-Activated Protein Kinases/metabolism ; Lipopolysaccharides/immunology ; MAP Kinase Kinase Kinases/metabolism ; MAP Kinase Signaling System ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; RNA Interference ; Signal Transduction ; Tumor Suppressor Proteins/genetics ; Ubiquitination ; p38 Mitogen-Activated Protein Kinases/metabolism |
| مستخلص: | 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. |
| معلومات مُعتمدة: | MOP 97744 Canada Canadian Institutes of Health Research |
| المشرفين على المادة: | 0 (Lipopolysaccharides) 0 (NF-kappa B) 0 (Sash1 protein, mouse) 0 (TNF Receptor-Associated Factor 6) 0 (Tlr4 protein, mouse) 0 (Toll-Like Receptor 4) 0 (Tumor Suppressor Proteins) EC 2.7.11.10 (Chuk protein, mouse) EC 2.7.11.10 (I-kappa B Kinase) EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) EC 2.7.11.25 (MAP Kinase Kinase Kinases) EC 2.7.11.25 (MAP kinase kinase kinase 7) |
| تواريخ الأحداث: | Date Created: 20130619 Date Completed: 20130918 Latest Revision: 20220408 |
| رمز التحديث: | 20231215 |
| DOI: | 10.4049/jimmunol.1200583 |
| PMID: | 23776175 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.1200583 |