JAKs and STATs in Immunity, Immunodeficiency, and Cancer

• Published in: The New England journal of medicine Vol. 368; no. 2; pp. 161 - 170
• Main Authors: O'Shea, John J, Holland, Steven M, Staudt, Louis M
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 10-01-2013
• Series: Mechanisms of Disease
• Subjects: Biological and medical sciences; Cytokines - metabolism; General aspects; Hematologic Diseases - drug therapy; Hematologic Diseases - genetics; Hematologic Diseases - physiopathology; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunologic Deficiency Syndromes - drug therapy; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - physiopathology; Immunopathology; Janus Kinases - antagonists & inhibitors; Janus Kinases - genetics; Janus Kinases - metabolism; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - physiopathology; Signal Transduction - drug effects; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; Tumors; Medicine; Jak protein tyrosine kinase; Immunopathology; Signal transduction; Transduction factor STAT; Malignant tumor; Immunity; Immune deficiency; Cancer
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMra1202117

A large number of cytokines signal through the JAK–STAT pathway. Abnormal function of this pathway may lead to a variety of diseases. Targeting the defects in this signaling pathway has already led to treatment advances, and further advances are likely.
This past year marked the 20th anniversary of the discovery of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway.
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Arising from efforts to understand the molecular mechanisms of interferon action, the elucidation of this pathway has provided many insights into disease mechanisms and has become the basis for new pharmacologic agents. It is therefore an appropriate time to take stock of our knowledge of this pathway and to consider the ways in which these insights are affecting the practice of medicine.
Cytokines and JAK–STAT Signaling
Interferons, erythropoietin, growth hormone, and prolactin, all discovered more than half a . . .