tyk2 kinase

Summary

Summary: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.

Top Publications

  1. Rattray M. New insights on regulation of LMTK2, a membrane kinase integrating pathways central to neurodegeneration. J Neurochem. 2012;121:327-8 pubmed publisher
  2. Doherty D, Bamshad M. Exome sequencing to find rare variants causing neurologic diseases. Neurology. 2012;79:396-7 pubmed publisher
  3. McNally R, Eck M. JAK-cytokine receptor recognition, unboxed. Nat Struct Mol Biol. 2014;21:431-3 pubmed publisher
  4. Hynes J, Wu H, Kempson J, Duan J, Lu Z, Jiang B, et al. Discovery of potent and efficacious pyrrolopyridazines as dual JAK1/3 inhibitors. Bioorg Med Chem Lett. 2017;27:3101-3106 pubmed publisher
    ..X-ray co-crystal structure determination confirmed the presumed inhibitor binding orientation in JAK3. Efforts to reduce hERG channel inhibition will be described. ..
  5. Lopez Rodriguez R, Hernández Bartolomé Á, Borque M, Rodríguez Muñoz Y, Martín Vílchez S, Garcia Buey L, et al. Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C. PLoS ONE. 2017;12:e0180927 pubmed publisher
    ..74). The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed. ..
  6. Herrmann A, Lahtz C, Nagao T, Song J, Chan W, Lee H, et al. CTLA4 Promotes Tyk2-STAT3-Dependent B-cell Oncogenicity. Cancer Res. 2017;77:5118-5128 pubmed publisher
    ..Overall, our results show how CTLA4-induced immune suppression occurs primarily via an intrinsic STAT3 pathway and that CTLA4 is critical for B-cell lymphoma proliferation and survival. Cancer Res; 77(18); 5118-28. ©2017 AACR. ..
  7. Liang J, van Abbema A, Balazs M, Barrett K, Berezhkovsky L, Blair W, et al. Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model. Bioorg Med Chem Lett. 2017;27:4370-4376 pubmed publisher
    ..In this efficacy model, the IL-17 decrease was accompanied by a reduction of ear thickness indicating the potential of TYK2 inhibition as a therapeutic approach for psoriasis patients. ..
  8. Wilbers R, van Raaij D, Westerhof L, Bakker J, Smant G, Schots A. Re-evaluation of IL-10 signaling reveals novel insights on the contribution of the intracellular domain of the IL-10R2 chain. PLoS ONE. 2017;12:e0186317 pubmed publisher
    ..This observation highlights a novel role for the intracellular domain of IL-10R2 in the molecular mechanisms of IL-10R activation. ..
  9. Babon J, Lucet I, Murphy J, Nicola N, Varghese L. The molecular regulation of Janus kinase (JAK) activation. Biochem J. 2014;462:1-13 pubmed publisher
    ..These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and suggest alternative therapeutic strategies to complement existing ATP-competitive kinase inhibitors. ..

More Information

Publications10

  1. Yamaji T, Shide K, Kameda T, Sekine M, Kamiunten A, Hidaka T, et al. Loss of Tyrosine Kinase 2 Does Not Affect the Severity of Jak2V617F-induced Murine Myeloproliferative Neoplasm. Anticancer Res. 2017;37:3841-3847 pubmed
    ..Upon JAK2 inhibitor therapy, both types of mice had equally improved leukocytosis and splenomegaly. TYK2 does not have cooperative effects with JAK2VF upon MPN onset nor in the presence of a JAK2 inhibitor. ..