Mechanisms and consequences of Jak-STAT signaling in the immune system.
Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced breakneck growth in the quarter century since its discovery and has yielded a stream of basic and clinical insights that have profoundly influenced modern understanding of human health and disease, exemplified by the bench-to-bedside success of Jak inhibitors ('jakinibs') and pathway-targeting drugs. Here we review recent advances in Jak-STAT biology, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Alejandro V
0000-0001-8068-2176
AV
Villarino
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Yuka
Y
Kanno
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
John J
JJ
O'Shea
D000818:Animals; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D005810:Multigene Family; D011485:Protein Binding; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical
D050791:STAT Transcription Factors; D053612:Janus Kinases