{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bittner ZA"],"funding":["German Research Foundation","University Hospital Tübingen","University of Tübingen","Deutsche Forschungsgemeinschaft","IFM Therapeutics","E-Rare program","Federal Ministry of Education and Research","Damon Runyon Cancer Research Foundation","Else-Kröner-Fresenius Stiftung"],"pagination":["e20201656"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8480672"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["218(11)"],"pubmed_abstract":["Activity of the NLRP3 inflammasome, a critical mediator of inflammation, is controlled by accessory proteins, posttranslational modifications, cellular localization, and oligomerization. How these factors relate is unclear. We show that a well-established drug target, Bruton's tyrosine kinase (BTK), affects several levels of NLRP3 regulation. BTK directly interacts with NLRP3 in immune cells and phosphorylates four conserved tyrosine residues upon inflammasome activation, in vitro and in vivo. Furthermore, BTK promotes NLRP3 relocalization, oligomerization, ASC polymerization, and full inflammasome assembly, probably by charge neutralization, upon modification of a polybasic linker known to direct NLRP3 Golgi association and inflammasome nucleation. As NLRP3 tyrosine modification by BTK al"],"journal":["The Journal of experimental medicine"],"pubmed_title":["BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome activity."],"pmcid":["PMC8480672"],"funding_grant_id":["CRC TR156","EXC 2180","EXC 2155 (39087428)","2615-0-0","EXC 2151 (390873048)","2310-0-0","GAIN_01GM1910A","EXC 2155","EXC 2180 (390900677)","EXC 2151","EXC 2189","EXC 2124","EXC 2189 (390939984)","We-4195/15-1","GR1617/14-1/iPAD"],"pubmed_authors":["Shankar S","Dickhofer S","Greve CL","Mangan M","Herster F","Cardona Gloria Y","Stevanovic S","Chang TH","Grimbacher B","Loffler MW","Delor A","Wu H","Liu X","Kalbacher H","Schilling NA","Scharl M","Spalinger M","Bittner ZA","Marcu A","Wolz OO","Weber ANR","Mateo Tortola M","Lovotti M","Wagner S","Duwell P","Kummerle-Deschner JB","Hantschel O","Andreeva L","Tapia-Abellan A","Bork F","Latz E","Bosch K"],"additional_accession":[]},"is_claimable":false,"name":"BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome activity.","description":"Activity of the NLRP3 inflammasome, a critical mediator of inflammation, is controlled by accessory proteins, posttranslational modifications, cellular localization, and oligomerization. How these factors relate is unclear. We show that a well-established drug target, Bruton's tyrosine kinase (BTK), affects several levels of NLRP3 regulation. BTK directly interacts with NLRP3 in immune cells and phosphorylates four conserved tyrosine residues upon inflammasome activation, in vitro and in vivo. Furthermore, BTK promotes NLRP3 relocalization, oligomerization, ASC polymerization, and full inflammasome assembly, probably by charge neutralization, upon modification of a polybasic linker known to direct NLRP3 Golgi association and inflammasome nucleation. As NLRP3 tyrosine modification by BTK al","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2026-05-31T06:06:29.704Z","creation":"2025-02-18T23:32:21.028Z"},"accession":"S-EPMC8480672","cross_references":{"pubmed":["34554188"],"doi":["10.1084/jem.20201656"]}}