This site is intended for U.S. Healthcare Professionals.

Healthcare professional standing in a field Healthcare professional standing in a field

IT’S TIME YOU KNOW ABOUT TYK2

Pathbreaking research is shedding light on the role of TYK2 in immunology

Certain immune-mediated diseases are characterized by the elevation of inflammatory cytokines regulated by several components. The tyrosine kinase 2 pathway plays a critical role in regulating certain triggers of inflammation involved in immune diseases.1,2

About TYK2

Know TYK2

Tyrosine kinase 2 (TYK2) is an intracellular enzyme involved in the relay of immune signals initiated by specific cytokines, including IL-23, IL-12 and Type I IFN.1,2

TYK2 is a central link between certain cytokines, such as IL-23, IL-12 and Type I IFN, and the downstream effects of these cytokines.3

Select each tile.

IL-23

TYK2 and JAK2 graphic
TYK2 and JAK2 graphic

IL-23 signaling through TYK2/JAK2 is critical in the expansion and survival of pathogenic Th17 cells as well as the induction of innate lymphoid cells in autoimmunity.4-6

IL-12

IL-12-induced TYK2/JAK2 activation initiates recruitment and phosphorylation of STAT4, which activates transcription of a major effector molecule in systemic immune disorders.4,5

IFNα, β

Activation by type I IFNs signaling through TYK2/JAK1 in the B cell impacts pathways important in autoimmunity such as B-cell differentiation, antibody production, and immunoglobulin isotype class switching.7

See the TYK2 pathway in action

TYK2 pathway video thumbnail

LEARN ABOUT THE PATHWAYS

Understand the differences

Cube icon

TYK2 and JAK1/2/3 are structurally different from each other8

The regulatory, or pseudokinase, domain of TYK2 and JAK1/2/3 are different from each other.8

TYK2 vs JAK protein graphic TYK2 vs JAK protein graphic

Active (ATP-binding) domain: similar across family members8

Gear icon

TYK2 and JAK1/2/3 are functionally different from each other9,10

TYK2 and JAK1/2/3 proteins form different dimers to mediate different sets of cytokine signals that can influence immune and/or systemic responses.9,10

TYK2 pathways vs JAK1/2/3 pathway graphic

The TYK2 and JAK1/2 pairs specifically mediate signals involved in immune functions2,3,10

JAK/JAK pairs mediate signals predominantly involved in both immune and broad systemic functions (eg, blood cell development, lipid metabolism)9-13

*Please note that this list of cytokines and effects modulated by the different TYK2/JAK and JAK/JAK pairs is not exhaustive. Certain cytokines might also be modulated by JAK and TYK2 trimers.2

ATP=adenosine triphosphate; EPO=erythropoietin; GH=growth hormone; GM-CSF=granulocyte-macrophage colony-stimulating factor; IFN=interferon; IL=interleukin; JAK=Janus kinase; TPO=thrombopoietin; TYK2=tyrosine kinase 2.

Emerging science

EXPLORING TYK2 RESEARCH

At BMS, we are committed to helping patients prevail over serious immune-related diseases such as psoriasis. We’re excited about our innovative research on the TYK2 pathway and the role it may play in immunology.

Download the TYK2 Fact Sheet
Healthcare professional standing Healthcare professional standing

References

  1. Mahil SK, Capon F, Barker JN. Update on psoriasis immunopathogenesis and targeted immunotherapy. Semin Immunopathol. 2016;38(1):11-27. doi:10.1007/s00281-015-0539-8
  2. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis? Ann Rheum Dis. 22018;77(2):175-187. doi:10.1136/annrheumdis-2017-211555
  3. Dendrou CA, Cortes A, Shipman L, et al. Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med. 2016;8:363ra149.
  4. 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(1):181-189. doi:10.4049/jimmunol.1003244
  5. Paunović V, Carroll HP, Vandenbroeck K, Gadina M. Signalling, inflammation and arthritis: crossed signals: the role of interleukin (IL)-12, -17, -23 and -27 in autoimmunity. Rheumatology (Oxford). 2008;47(6):771-776. doi:10.1093/rheumatology/kem352
  6. Geremia A, Arancibia-Cárcamo CV, Fleming MPP, et al. IL-23—responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med. 2011;208(6):1127-1133. doi:10.1084/jem.20101712
  7. Rönnblom L, Eloranta ML, Alm GV. The type I interferon system in systemic lupus erythematosus. Arthritis Rheum. 2006;54(2):408-420. doi:10.1002/art.21571
  8. Tokarski JS, Zupa-Fernandez A, Tredup JA, et al. Tyrosine kinase 2-mediated signal transduction in T lymphocytes is blocked by pharmacological stabilization of its pseudokinase domain. J Biol Chem. 2015;290(17):11061-11074. doi:10.1074/jbc.M114.619502
  9. Hammarén HM, Virtanen AT, Raivola J, Silvennoinen O. The regulation of JAKs in cytokine signaling and its breakdown in disease. Cytokine. 2019;118:48-63. doi.org/10.1016/j.cyto.2018.03.041
  10. Morris R, Kershaw NJ, Babon JJ. The molecular details of cytokine signaling via the JAK/STAT pathway. Protein Sci. 2018;27:1984-2009. doi:10.1002/pro.3519
  11. Xu D, Yin C, Wang S, Xiao Y. JAK-STAT in lipid metabolism of adipocytes. JAKSTAT. 2013;2(4):e27203. doi:10.4161/jkst.27203
  12. Jiang L, Li Z, Rui L. Leptin stimulates both JAK2-dependent and JAK2-independent signaling pathways. J Biol Chem. 2008;283:28066-28073. doi:10.1074/jbc.M805545200
  13. Richard AJ, Stephens JM. Emerging roles of JAK-STAT signaling pathways in adipocytes. Trends Endocrinol Metab. 2011;22:325-332.