| http://purl.uniprot.org/citations/21965679 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21965679 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21965679 | http://www.w3.org/2000/01/rdf-schema#comment | "IL-36α, IL-36β, and IL-36γ (formerly IL-1F6, IL-1F8, and IL-1F9) are IL-1 family members that signal through the IL-1 receptor family members IL-1Rrp2 (IL-1RL2) and IL-1RAcP. IL-36Ra (formerly IL-1F5) has been reported to antagonize IL-36γ. However, our previous attempts to demonstrate IL-36Ra antagonism were unsuccessful. Here, we demonstrate that IL-36Ra antagonist activity is dependent upon removal of its N-terminal methionine. IL-36Ra starting at Val-2 is fully active and capable of inhibiting not only IL-36γ but also IL-36α and IL-36β. Val-2 of IL-36Ra lies 9 amino acids N-terminal to an A-X-Asp motif conserved in all IL-1 family members. In further experiments, we show that truncation of IL-36α, IL-36β, and IL-36γ to this same point increased their specific activity by ∼10(3)-10(4)-fold (from EC(50) 1 μg/ml to EC(50) 1 ng/ml). Inhibition of truncated IL-36β activity required ∼10(2)-10(3)-fold excess IL-36Ra, similar to the ratio required for IL-1Ra to inhibit IL-1β. Chimeric receptor experiments demonstrated that the extracellular (but not cytoplasmic) domain of IL-1Rrp2 or IL-1R1 is required for inhibition by their respective natural antagonists. IL-36Ra bound to IL-1Rrp2, and pretreatment of IL-1Rrp2-expressing cells with IL-36Ra prevented IL-36β-mediated co-immunoprecipitation of IL-1Rrp2 with IL-1RAcP. Taken together, these results suggest that the mechanism of IL-36Ra antagonism is analogous to that of IL-1Ra, such that IL-36Ra binds to IL-1Rrp2 and prevents IL-1RAcP recruitment and the formation of a functional signaling complex. In addition, truncation of IL-36α, IL-36β, and IL-36γ dramatically enhances their activity, suggesting that post-translational processing is required for full activity."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.267922"xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.267922"xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Shen M."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Shen M."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Douangpanya J."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Douangpanya J."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Sims J.E."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Sims J.E."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Towne J.E."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Towne J.E."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Lipsky B.P."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Lipsky B.P."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Gabel C.A."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Gabel C.A."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Renshaw B.R."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/author | "Renshaw B.R."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/pages | "42594-42602"xsd:string |
| http://purl.uniprot.org/citations/21965679 | http://purl.uniprot.org/core/pages | "42594-42602"xsd:string |