کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1964783 | 1058594 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Protein phosphatase 2A carboxymethylation and regulatory B subunits differentially regulate mast cell degranulation
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کلمات کلیدی
shRNAERKPP2AIgEPKCβ-hexMAPK - MAPKp38 MAP kinase - p38 mAP kinaseshort hairpin RNA - RNA موی سر کوتاهβ-hexosaminidase - β-هگزوسامینیدازAsthma - آسمOkadaic acid - اسید اوکادائیک IgE, immunoglobulin E - ایمونوگلوبولین Eextracellular signal regulated kinases - سیگنال خارج سلولی kinases را تنظیم می کندDegranulation - قرمزی چشمMast cell - ماستسلProtein phosphatase - پروتئین فسفاتازProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogen
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Asthma is characterised by antigen-mediated mast cell degranulation resulting in secretion of inflammatory mediators. Protein phosphatase 2A (PP2A) is a serine/threonine protein phosphatase composed of a catalytic (PP2A-C) subunit together with a core scaffold (PP2A-A) subunit and a variable, regulatory (PP2A-B) subunit. Previous studies utilising pharmacological inhibition of protein phosphatases have suggested a positive regulatory role for PP2A in mast cell degranulation. In support of this we find that a high okadaic acid concentration (1 μM) inhibits mast cell degranulation. Strikingly, we now show that a low concentration of okadaic acid (0.1 μM) has the opposite effect, resulting in enhanced degranulation. Selective downregulation of the PP2A-Cα subunit by short hairpin RNA also enhanced degranulation of RBL-2H3 mast cells, suggesting that the primary role of PP2A is to negatively regulate degranulation. PP2A-B subunits are responsible for substrate specificity, and carboxymethylation of the PP2A-C subunit alters B subunit binding. We show here that carboxymethylation of PP2A-C is dynamically altered during degranulation and inhibition of methylation decreases degranulation. Moreover downregulation of the PP2A-Bα subunit resulted in decreased MK2 phosphorylation and degranulation, whilst downregulation of the PP2A-Bâ²Î´ subunit enhanced p38 MAPK phosphorylation and degranulation. Taken together these data show that PP2A is both a positive and negative regulator of mast cell degranulation, and this differential role is regulated by carboxymethylation and specific PP2A-B subunit binding.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 22, Issue 12, December 2010, Pages 1882-1890
Journal: Cellular Signalling - Volume 22, Issue 12, December 2010, Pages 1882-1890
نویسندگان
Gregory Kranias, Lauren F. Watt, Helen Carpenter, Jeff Holst, Russell Ludowyke, Stefan Strack, Alistair T.R. Sim, Nicole M. Verrills,