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000139309 0247_ $$2doi$$a10.1084/jem.20160933
000139309 0247_ $$2pmid$$apmid:28465465
000139309 0247_ $$2pmc$$apmc:PMC5460996
000139309 0247_ $$2ISSN$$a0022-1007
000139309 0247_ $$2ISSN$$a1540-9358
000139309 0247_ $$2ISSN$$a1540-9538
000139309 0247_ $$2altmetric$$aaltmetric:19847353
000139309 037__ $$aDZNE-2020-05631
000139309 041__ $$aEnglish
000139309 082__ $$a610
000139309 1001_ $$aStutz, Andrea$$b0
000139309 245__ $$aNLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin domain.
000139309 260__ $$aNew York, NY$$bRockefeller Univ. Press$$c2017
000139309 264_1 $$2Crossref$$3online$$bRockefeller University Press$$c2017-05-02
000139309 264_1 $$2Crossref$$3print$$bRockefeller University Press$$c2017-06-05
000139309 3367_ $$2DRIVER$$aarticle
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000139309 3367_ $$2BibTeX$$aARTICLE
000139309 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000139309 3367_ $$00$$2EndNote$$aJournal Article
000139309 520__ $$aNLRP3 is a cytosolic pattern recognition receptor that senses microbes and endogenous danger signals. Upon activation, NLRP3 forms an inflammasome with the adapter ASC, resulting in caspase-1 activation, release of proinflammatory cytokines and cell death. How NLRP3 activation is regulated by transcriptional and posttranslational mechanisms to prevent aberrant activation remains incompletely understood. Here, we identify three conserved phosphorylation sites in NLRP3 and demonstrate that NLRP3 activation is controlled by phosphorylation of its pyrin domain (PYD). Phosphomimetic residues in NLRP3 PYD abrogate inflammasome activation and structural modeling indicates that phosphorylation of the PYD regulates charge-charge interaction between two PYDs that are essential for NLRP3 activation. Phosphatase 2A (PP2A) inhibition or knock-down drastically reduces NLRP3 activation, showing that PP2A can license inflammasome assembly via dephosphorylating NLRP3 PYD. These results propose that the balance between kinases and phosphatases acting on the NLRP3 PYD is critical for NLRP3 activation.
000139309 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000139309 542__ $$2Crossref$$i2019-09-19$$uhttp://www.rupress.org/terms/
000139309 542__ $$2Crossref$$i2017-12-04$$uhttps://creativecommons.org/licenses/by-nc-sa/4.0/
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000139309 650_7 $$2NLM Chemicals$$aInflammasomes
000139309 650_7 $$2NLM Chemicals$$aNLR Family, Pyrin Domain-Containing 3 Protein
000139309 650_7 $$2NLM Chemicals$$aNlrp3 protein, mouse
000139309 650_7 $$2NLM Chemicals$$aPyrin
000139309 650_7 $$017885-08-4$$2NLM Chemicals$$aPhosphoserine
000139309 650_7 $$0EC 3.1.3.16$$2NLM Chemicals$$aProtein Phosphatase 2
000139309 650_2 $$2MeSH$$aAmino Acid Sequence
000139309 650_2 $$2MeSH$$aAnimals
000139309 650_2 $$2MeSH$$aHEK293 Cells
000139309 650_2 $$2MeSH$$aHumans
000139309 650_2 $$2MeSH$$aInflammasomes: metabolism
000139309 650_2 $$2MeSH$$aMice
000139309 650_2 $$2MeSH$$aModels, Biological
000139309 650_2 $$2MeSH$$aModels, Molecular
000139309 650_2 $$2MeSH$$aNLR Family, Pyrin Domain-Containing 3 Protein: chemistry
000139309 650_2 $$2MeSH$$aNLR Family, Pyrin Domain-Containing 3 Protein: metabolism
000139309 650_2 $$2MeSH$$aPhosphorylation
000139309 650_2 $$2MeSH$$aPhosphoserine: metabolism
000139309 650_2 $$2MeSH$$aProtein Binding
000139309 650_2 $$2MeSH$$aProtein Domains
000139309 650_2 $$2MeSH$$aProtein Phosphatase 2: metabolism
000139309 650_2 $$2MeSH$$aPyrin: chemistry
000139309 650_2 $$2MeSH$$aStructure-Activity Relationship
000139309 7001_ $$aKolbe, Carl-Christian$$b1
000139309 7001_ $$aStahl, Rainer$$b2
000139309 7001_ $$aHorvath, Gabor L$$b3
000139309 7001_ $$0P:(DE-HGF)0$$aFranklin, Bernardo S$$b4
000139309 7001_ $$avan Ray, Olivia$$b5
000139309 7001_ $$aBrinkschulte, Rebecca$$b6
000139309 7001_ $$aGeyer, Matthias$$b7
000139309 7001_ $$aMeissner, Felix$$b8
000139309 7001_ $$0P:(DE-2719)2000062$$aLatz, Eicke$$b9$$eLast author$$udzne
000139309 77318 $$2Crossref$$3journal-article$$a10.1084/jem.20160933$$b : Rockefeller University Press, 2017-05-02$$n6$$p1725-1736$$tJournal of Experimental Medicine$$v214$$x0022-1007$$y2017
000139309 773__ $$0PERI:(DE-600)1477240-1$$a10.1084/jem.20160933$$gVol. 214, no. 6, p. 1725 - 1736$$n6$$p1725-1736$$q214:6<1725 - 1736$$tJournal of experimental medicine$$v214$$x0022-1007$$y2017
000139309 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460996
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000139309 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000062$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b9$$kDZNE
000139309 9131_ $$0G:(DE-HGF)POF3-342$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$aDE-HGF$$bForschungsbereich Gesundheit$$lErkrankungen des Nervensystems$$vDisease Mechanisms and Model Systems$$x0
000139309 9141_ $$y2017
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