| http://purl.uniprot.org/citations/30104382 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30104382 | http://www.w3.org/2000/01/rdf-schema#comment | "Thioredoxin 1 (TRX), an essential intracellular redox regulator, is also secreted by mammalian cells. Recently, we showed that TRX activates extracellular transglutaminase 2 via reduction of an allosteric disulfide bond. In an effort to identify other extracellular substrates of TRX, macrophages derived from THP-1 cells were treated with NP161, a small-molecule inhibitor of secreted TRX. NP161 enhanced cytokine outputs of alternatively activated macrophages, suggesting that extracellular TRX regulated the activity of interleukin 4 (IL-4) and/or interleukin 13 (IL-13). To test this hypothesis, the C35S mutant of human TRX was shown to form a mixed disulfide bond with recombinant IL-4 but not IL-13. Kinetic analysis revealed a kcat/KM value of 8.1 μM-1⋅min-1 for TRX-mediated recognition of IL-4, which established this cytokine as the most selective partner of extracellular TRX to date. Mass spectrometry identified the C46-C99 bond of IL-4 as the target of TRX, consistent with the essential role of this disulfide bond in IL-4 activity. To demonstrate the physiological relevance of our biochemical findings, recombinant TRX was shown to attenuate IL-4-dependent proliferation of cultured TF-1 erythroleukemia cells and also to inhibit the progression of chronic pancreatitis in an IL-4-driven mouse model of this disease. By establishing that IL-4 is posttranslationally regulated by TRX-promoted reduction of a disulfide bond, our findings highlight a novel regulatory mechanism of the type 2 immune response that is specific to IL-4 over IL-13."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1805288115"xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/author | "Zhao Q."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/author | "Khosla C."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/author | "Palanski B.A."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/author | "Habtezion A."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/author | "Weng N."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/author | "Maecker H.T."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/author | "Plugis N.M."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/pages | "8781-8786"xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/title | "Interleukin 4 is inactivated via selective disulfide-bond reduction by extracellular thioredoxin."xsd:string |
| http://purl.uniprot.org/citations/30104382 | http://purl.uniprot.org/core/volume | "115"xsd:string |
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