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TYK2
Tyrosine Kinase 2

TYK2
Tyrosine Kinase 2

Overview

Tyrosine kinase 2 (TYK2) is a kinase that is part of the Janus kinase (JAK) family of kinases. The intracellular kinases are ubiquitously expressed in tissues as dimer pairs and cross phosphorylate as a result of extracellular cytokine-receptor engagement. TYK2 and its corresponding dimer pair then activate a series of transcription factors called signal transducer and activator of transcription (STAT). Activated STATs promote expression of cytokines and cellular processes such as cellular division, differentiation, and death.1

  • IL-12-induced TYK2 activation initiates recruitment and phosphorylation of STAT4 which activates transcription of a major effector molecule in systemic immune disorders.2,3
  • IL-23 signaling through TYK2 is critical in the expansion and survival of pathogenic TH17 cells as well as the induction of innate lymphoid cells in autoimmunity.3,4
  • Activation by type I IFNs signaling through TYK2 in the B cell impacts pathways important in autoimmunity such as B-cell differentiation, antibody production, and immunoglobulin isotype class switching.5
TYK2 Pathway

References

  1. Leitner NR, et al. Tyrosine kinase 2 – Surveillant of tumors and bona fide oncogene. Cytokine. 2017;89:209-218.
  2. Ishizaki M, Akimoto T, Muromoto R, et al. Involvement of tyrosine kinase-2 in both the IL-12/Th1 and IL-23/Th17 Axes in vivo. J Immunol. 2011;187:181-189.
  3. Paunovic V, Vandenbroeck CK, Gadina M. Crossed signals: the role of interleukin (IL)-12, -17, -23 and -27 in autoimmunity. Rheumatology. 2008;47:771-776.
  4. Geremia A, Arancibia-Carcamo CV, Fleming MPP, et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med. 208(6):1127-1133.
  5. Ronnblom L, Eloranta M-L, Alm GV. The type I interferon system in systemic lupus erythematosus. Arthritis Rheum. 2006;54(2):408-420.