{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wilmes S"],"funding":["University of Leeds","DFG","Horizon 2020 Framework Programme","EMBO","NHLBI NIH HHS","National Heart, Lung, and Blood Institute","EPSRC","Wellcome Trust","Engineering and Physical Sciences Research Council"],"pagination":["e66014"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8099432"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10"],"pubmed_abstract":["Cytokines elicit pleiotropic and non-redundant activities despite strong overlap in their usage of receptors, JAKs and STATs molecules. We use IL-6 and IL-27 to ask how two cytokines activating the same signaling pathway have different biological roles. We found that IL-27 induces more sustained STAT1 phosphorylation than IL-6, with the two cytokines inducing comparable levels of STAT3 phosphorylation. Mathematical and statistical modeling of IL-6 and IL-27 signaling identified STAT3 binding to GP130, and STAT1 binding to IL-27Rα, as the main dynamical processes contributing to sustained pSTAT1 levels by IL-27. Mutation of Tyr613 on IL-27Rα decreased IL-27-induced STAT1 phosphorylation by 80% but had limited effect on STAT3 phosphorgylation. Strong receptor/STAT coupling by IL-27 initiated"],"journal":["eLife"],"pubmed_title":["Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses."],"pmcid":["PMC8099432"],"funding_grant_id":["714680","K22HL125593","SFB 944, P8/Z","454–2017","K22 HL125593","202323/Z/16/Z","764698","ERC-206-STG","1969354"],"pubmed_authors":["Lopez-Garcia M","Moraga I","Piehler J","Lythe G","Martinez-Fabregas J","Gaggero S","Guerrier T","Launay D","Fyfe PK","Hafer M","Molina-Paris C","Taylor C","Wilmes S","Jeffrey PA","Pohler E","Mitra S"],"additional_accession":[]},"is_claimable":false,"name":"Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses.","description":"Cytokines elicit pleiotropic and non-redundant activities despite strong overlap in their usage of receptors, JAKs and STATs molecules. We use IL-6 and IL-27 to ask how two cytokines activating the same signaling pathway have different biological roles. We found that IL-27 induces more sustained STAT1 phosphorylation than IL-6, with the two cytokines inducing comparable levels of STAT3 phosphorylation. Mathematical and statistical modeling of IL-6 and IL-27 signaling identified STAT3 binding to GP130, and STAT1 binding to IL-27Rα, as the main dynamical processes contributing to sustained pSTAT1 levels by IL-27. Mutation of Tyr613 on IL-27Rα decreased IL-27-induced STAT1 phosphorylation by 80% but had limited effect on STAT3 phosphorgylation. Strong receptor/STAT coupling by IL-27 initiated","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2026-05-10T02:48:44.383Z","creation":"2022-02-10T14:04:36.524Z"},"accession":"S-EPMC8099432","cross_references":{"pubmed":["33871355"],"doi":["10.7554/eLife.66014"]}}