title: Mechanisms of Jak/STAT signaling in immunity and disease.
abstract: More than two decades ago, experiments on the antiviral mechanisms of IFNs led to the discovery of JAKs and their downstream effectors, the STAT proteins. This pathway has since become a paradigm for membrane-to-nucleus signaling and explains how a broad range of soluble factors, including cytokines and hormones, mediate their diverse functions. Jak/STAT research has not only impacted basic science, particularly in the context of intercellular communication and cell-extrinsic control of gene expression, it also has become a prototype for transition from bench to bedside, culminating in the development and clinical implementation of pathway-specific therapeutics. This brief review synthesizes our current understanding of Jak/STAT biology while taking stock of the lessons learned and the challenges that lie ahead.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Alejandro V
authors.initials: AV
authors.lastname: Villarino
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: John R
authors.initials: JR
authors.lastname: Ferdinand
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 osheaj@arb.niams.nih.gov.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007109:Immunity; D053612:Janus Kinases / Q000276:immunology*; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000276:immunology*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D050791:STAT Transcription Factors; D053612:Janus Kinases