کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1964242 | 1058536 | 2008 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
G-protein-dependent and -independent pathways regulate proteinase-activated receptor-2 mediated p65 NFκB serine 536 phosphorylation in human keratinocytes
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کلمات کلیدی
TNFαRhoGEFGq/11Regulators of G-protein signallinginhibitory kappa B kinaseNHEKHTLVphorbol 12-myristate 13-acetateRGSPAR-2IKKPKCTLRGPCRLSCJnkERKc-Jun N-terminal protein kinase - C-Jun N-terminal protein kinaseG-protein-coupled receptors - G-پروتئین گیرندهPMA - LDC هاNFκB - NFKBPI3 kinase - PI3 کینازRNAi - RNA سرکوبگر،RNA مداخلهگر، RNA خاموش کنندهsiRNA - siRNAadenoviral - آدنویروئالsmall interfering ribonucleic acid - اسید ریبونوکلئیک دخالت کندinflammation - التهاب( توروم) ribonucleic acid interference - تداخل اسید ریبونوکلئیکtumour necrosis factor-alpha - تومور نکروز عامل آلفاRelA - رالاnuclear factor kappa B - فاکتور هسته ای کاپا BPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenproteinase-activated receptor-2 - پروتئیناز فعال گیرنده-2MAP kinase - کیناز MAPextracellular signal-related kinase - کیناز مرتبط با سیگنال خارج سلولیToll-like receptors - گیرنده های پولی مانند
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The mechanisms underpinning the coupling of GPCRs, such as PAR-2, to the phosphorylation of p65 NFκB have not been investigated. In the current study we found that trypsin and the selective PAR-2 activating peptide, 2f-LIGKV-OH, stimulated large and sustained increases in the serine 536 phosphorylation of p65/RelA in a transfected skin epithelial cell line and primary keratinocytes. Parallel experiments showed that in both cell types, p65 NFκB phosphorylation is mediated through the selective activation of IKK2. Treatment with PKC inhibitor GF109203X or PKCα siRNA reduced phosphorylation at 15 min but not 30 min, whilst rottlerin, a selective PKCδ inhibitor and PKCδ siRNA reduced the response at both time points. Pre-treatment of cells with the novel Gq/11 inhibitor YM-254890 and Gq/11 siRNA caused a similar pattern of inhibition and also reduced PAR-2-mediated NFκB transcriptional activity. Furthermore, stimulation of cells through a novel PAR-2 mutant PAR-234-43, delayed p65 phosphorylation but was without effect on the kinetics of ERK activation. Inhibition of Gi or G12/13 pathways by pertussis toxin pre-treatment or over-expression of the RGS mutant Lsc, also did not effect NFκB phosphorylation. Taken together these data indicate dependency for Gq/11 in early phosphorylation of p65 NFκB and this subsequently affects initial NFκB-dependent gene transcriptional activity, however later regulation of p65 is unaffected. Overall these novel data demonstrate an IKK2-dependent, predominantly G-protein-independent pathway involved in PAR-2 regulation of NFκB phosphorylation in keratinocytes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 20, Issue 7, July 2008, Pages 1267-1274
Journal: Cellular Signalling - Volume 20, Issue 7, July 2008, Pages 1267-1274
نویسندگان
Fui Goon Goh, Callum M. Sloss, Margaret R. Cunningham, Mary Nilsson, Laurence Cadalbert, Robin Plevin,