Definition
Janus kinases transduce signals emanating from dozens of extracellular cytokines inside the cell by activating their downstream effectors such as STAT transcription factors. JAKs regulate critical cellular functions such as survival, proliferation, homeostasis, and immune and inflammatory responses. On the other hand, JAKs participate in the pathogenesis of several immunological and inflammatory diseases. Activating JAK mutations cause hematological diseases and cancers, and inactivating JAK mutations lead to immunodeficiencies. Currently, JAK inhibitors (JAKi) are used for the treatment of myeloproliferative neoplasms, rheumatoid or psoriatic arthritis, and inflammatory bowel disease, and clinical trials are ongoing for a wide range of other autoimmune and malignant diseases.
Basic Characteristics
Janus Kinases and the Cytokine Signaling
Janus kinases (JAKs) are nonreceptor tyrosine kinases that catalyze the transfer...
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References
Babon JJ et al (2014) The molecular regulation of Janus kinase (JAK) activation. Biochem J 462(1):1–13. https://doi.org/10.1042/BJ20140712. England
Bewersdorf JP et al (2019) Beyond Ruxolitinib: Fedratinib and other emergent treatment options for myelofibrosis. Cancer Manag Res 11:10777–10790. https://doi.org/10.2147/CMAR.S212559. New Zealand.
Biggioggero M et al (2019) Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis. Drugs in context 8:212595. https://doi.org/10.7573/dic.212595. England
ClinicalTrials.gov (2020, June). Available at: https://clinicaltrials.gov/.
Hammaren HM et al (2019) The regulation of JAKs in cytokine signaling and its breakdown in disease. Cytokine 118:48–63. https://doi.org/10.1016/j.cyto.2018.03.041. England
Markham A, Keam SJ (2019) Peficitinib: first global approval. Drugs 79(8):887–891. https://doi.org/10.1007/s40265-019-01131-y. New Zealand
Pfizer (2019) Pfizer initiates phase 2B/3 clinical trial PF-06651600, an oral JAK3 inhibitor, for the treatment of patients with moderate to severe alopecia areata. Available at: https://investors.pfizer.com/investor-news/press-release-details/2019/Pfizer-Initiates-Phase-2b3-Clinical-Trial-for-PF-06651600-an-Oral-JAK3-Inhibitor-for-the-Treatment-of-Patients-with-Moderate-to-Severe-Alopecia-Areata/default.aspx
Plosker GL (2014) Sitagliptin: a review of its use in patients with type 2 diabetes mellitus. Drugs 74(2):223–242. https://doi.org/10.1007/s40265-013-0169-1. New Zealand
Rawlings JS, Rosler KM, Harrison DA (2004) The JAK/STAT signaling pathway. J Cell Sci 117(Pt 8):1281–1283. https://doi.org/10.1242/jcs.00963. England
Saharinen P, Silvennoinen O (2002) The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. J Biol Chem 277(49):47954–47963. https://doi.org/10.1074/jbc.M205156200. USA
Salgado E, Gómez-Reino J (2013) The JAK inhibitor tofacitinib for active rheumatoid arthritis: Results from Phase III trials. Int J Clin Rheumatol 8:315–326. https://doi.org/10.2217/ijr.13.26
Silvennoinen O, Hubbard SR (2015) Molecular insights into regulation of JAK2 in myeloproliferative neoplasms. Blood 125(22):3388–3392. https://doi.org/10.1182/blood-2015-01-621110. USA
Taylor PC et al (2017) Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 376(7):652–662. https://doi.org/10.1056/NEJMoa1608345. Massachusetts Medical Society.
Ungureanu D et al (2011) The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat Struct Mol Biol 18(9):971–976. https://doi.org/10.1038/nsmb.2099. USA
Vainchenker W, Constantinescu SN (2013) JAK/STAT signaling in hematological malignancies. Oncogene 32(21):2601–2613. https://doi.org/10.1038/onc.2012.347. England
Virtanen AT et al (2019) Selective JAKinibs: prospects in inflammatory and autoimmune diseases. BioDrugs 33(1):15–32. https://doi.org/10.1007/s40259-019-00333-w. New Zealand
Wernig G et al (2008) Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell 13(4):311–320. https://doi.org/10.1016/j.ccr.2008.02.009. USA
Wilmes S et al (2020) Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations. Science 367(6478):643–652. https://doi.org/10.1126/science.aaw3242
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George Abraham, B., Raivola, J., Virtanen, A., Silvennoinen, O. (2021). Janus Kinase. In: Offermanns, S., Rosenthal, W. (eds) Encyclopedia of Molecular Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-030-57401-7_10072
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DOI: https://doi.org/10.1007/978-3-030-57401-7_10072
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