کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8308957 | 1538501 | 2018 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
AKT1 distinctively suppresses MyD88-depenedent and TRIF-dependent Toll-like receptor signaling in a kinase activity-independent manner
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کلمات کلیدی
Pam3CSK4phosphatidylinositol (3,4,5) trisphosphateIL-1R-associated kinasePIP3ISGIRF3NF-κBAkt1TLRoligodeoxynucleotideODNLPSMALP-2 - Malpas-2TRIF - Trif بهinterferon stimulated gene - اینترفرون ژن تحریک می شودToll-like receptor - تیالآرIRAK - عراقlipopolysaccharide - لیپوپلی ساکاریدknock out - ناک اوتPleckstrin Homology - همخوانی Pleckstrinkinase-dead - کیناز مرده است
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: AKT1 distinctively suppresses MyD88-depenedent and TRIF-dependent Toll-like receptor signaling in a kinase activity-independent manner AKT1 distinctively suppresses MyD88-depenedent and TRIF-dependent Toll-like receptor signaling in a kinase activity-independent manner](/preview/png/8308957.png)
چکیده انگلیسی
We found that AKT1, a primary effector molecule of PI3K-AKT signaling, distinctively suppressed Toll-like receptor (TLR)-mediated MyD88-dependent and Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling by inhibiting NF-κB activation and IRF3 activity independently of its kinase activity. In AKT1 knockout RAW264.7 cells, lipopolysaccharide (LPS)-induced transcription and protein production of cytokines including IL-1β and TNF-α (regulated by the MyD88-dependent pathway), as well as IFN-β and RANTES (C-C motif chemokine ligand 5: CCL-5; regulated by the TRIF-dependent pathways) was enhanced compared to wild type cells. In response to LPS stimulation, AKT1 knockout cells also exhibited enhanced NF-κB and IFN-β promoter activities, which were reduced to a level comparable to that in wild type cells by complementation with either AKT1 or its kinase-dead mutant (AKT1-KD). Expression of AKT1 or AKT1-KD similarly suppressed NF-κB and IFN-β promoter activities induced by LPS and other TLR ligands in wild type cells. Analysis of NF-κB activation caused by transient expression of proteins involved in the MyD88-dependent pathway in TLR signaling revealed that AKT1 suppressed signaling that occurs between activation of IKKβ and that of NF-κB. In contrast, AKT1 appeared to suppress the IFN-β promoter through inhibition of IRF3 activity itself. These results demonstrate a novel, non-kinase function of AKT1 that inhibits TLR signaling, and suggest the multifunctional nature of AKT1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 43, March 2018, Pages 32-39
Journal: Cellular Signalling - Volume 43, March 2018, Pages 32-39
نویسندگان
Kosuke Zenke, Masashi Muroi, Ken-ichi Tanamoto,