title: The JAK-STAT pathway: impact on human disease and therapeutic intervention.
abstract: The Janus kinase (JAK)-signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. This pathway provides an elegant and remarkably straightforward mechanism whereby extracellular factors control gene expression. It thus serves as a fundamental paradigm for how cells sense environmental cues and interpret these signals to regulate cell growth and differentiation. Genetic mutations and polymorphisms are functionally relevant to a variety of human diseases, especially cancer and immune-related conditions. The clinical relevance of the pathway has been confirmed by the emergence of a new class of therapeutics that targets JAKs.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892; email: osheajo@mail.nih.gov.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: Daniella M
authors.initials: DM
authors.lastname: Schwartz
authors.forename: Alejandro V
authors.initials: AV
authors.lastname: Villarino
authors.forename: Massimo
authors.initials: M
authors.lastname: Gadina
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
mesh_terms: D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D053612:Janus Kinases / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics*; D050791:STAT Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases
keywords: autoimmunity; cancer; cytokine; immunodeficiency; kinase inhibitors