The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention

• Published in: Annual review of medicine Vol. 66; no. 1; pp. 311 - 328
• Main Authors: O'Shea, John J, Schwartz, Daniella M, Villarino, Alejandro V, Gadina, Massimo, McInnes, Iain B, Laurence, Arian
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 01-01-2015; Annual Reviews, Inc
• Subjects: autoimmunity; cancer; Cellular biology; cytokine; Disease; Gene expression; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; immunodeficiency; Immunologic Deficiency Syndromes - genetics; Janus Kinases - genetics; Janus Kinases - metabolism; kinase inhibitors; Kinases; Mutation; Neoplasms - genetics; Polymorphism; Signal Transduction; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; cytokine; cancer; immunodeficiency; kinase inhibitors; autoimmunity
• ISSN: 0066-4219; 1545-326X
• DOI: 10.1146/annurev-med-051113-024537

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.