The JAK-STAT Pathway at Twenty

By G. Stark, James E. Darnell. Immunity, 2012

1,455 citations recorded by the source corpus.

We look back on the discoveries that the tyrosine kinases TYK2 and JAK1 and the transcription factors STAT1, STAT2, and IRF9 are required for the cellular response to type I interferons. This initial description of the JAK-STAT pathway led quickly to additional discoveries that type II interferons and many other cytokines signal through similar mechanisms. This well-understood pathway now serves as a paradigm showing how information from protein-protein contacts at the cell surface can be conveyed directly to genes in the nucleus. We also review recent work on the STAT proteins showing the importance of several different posttranslational modifications, including serine phosphorylation, acetylation, methylation, and sumoylation. These remarkably proficient proteins also provide noncanonical functions in transcriptional regulation and they also function in mitochondrial respiration and chromatin organization in ways that may not involve transcription at all.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/96c4ebc0be0ef5583b21365ed40f8a42804d8516

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Citations in the corpus

Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection (2021, background): “The ISGF3 complex then rapidly translocates into the nucleus in an importindependent manner and binds to IFN-stimulated response elements of IFN-stimulated genes to activate their transcription (98) (Fig.”
The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells (2017, background): “Type I- and II receptors are constitutively associated with JAKs [12].”
Interferon-Stimulated Genes: A Complex Web of Host Defenses (2014, background): “For a more thorough account of the events that occur during JAK-STAT signaling and the important discoveries that led to elucidation of the pathway, the reader is referred to a recent review (1).”
STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain (2013, background): “Constitutively activated STAT3 mediates deregulated growth, survival, and angiogenesis (2, 3).”
JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. (2012, background): “As discussed by Stark and Darnell (2012) in this issue, the discovery of Janus kinases and of signal transducers and activators of transcription (JAKs and STATs) stemmed from attempts to understand how IFNs exerted their effect.”
Parsing the interferon transcriptional network and its disease associations (2016, positive): “The receptor subunits are associated with JAK1 and TYK2 kinases, whose activation results in phosphorylation of STAT1 and STAT2 transducers, which then associate with IRF9 to form the ISGF3 complex which activates ISG transcription (Stark and Darnell, Jr., 2012).”
IL-6 in inflammation, autoimmunity and cancer (2020, background): “Activated JAK phos-phorylates tyrosine residues in the cytoplasmic domain of gp130 (30, 31, 61, 62, 102, 103).”
The molecular details of cytokine signaling via the JAK/STAT pathway (2018, background): “The molecular details of the JAK/STAT pathway were largely uncovered in a series of ground breaking studies from the laboratories of James Darnell, George Stark and Ian Kerr more than two decades ago.(1) It is an elegantly simple signaling cascade in which the cytokine requires only three components”
Mechanisms and consequences of Jak-STAT signaling in the immune system (2017, background): “In contrast, lineage-restricted deletion of Jaks has not been widely adopted despite the severe developmental and immunological defects observed in knockout mice.”