TYK2 JH2 Domain (human, recombinant; aa 575-869)

Tyrosine kinase 2 (TYK2) is a member of the JAK family of non-receptor tyrosine kinases that has a key role in cytokine signaling.^1,2 It is composed of an N-terminal FERM homology domain, which mediates protein-protein interactions, a Src-homology 2 (SH2) domain, an autoinhibitory and catalytically inactive pseudokinase domain (JH2), and a C-terminal kinase domain.¹ TYK2 is expressed by a variety of immune cells, including T cells, B cells, dendritic cells, mast cells, and macrophages, where it associates with numerous cytokine receptor chains, including IFN-α/β receptor 1 (IFNAR1), IL-12Rβ1, IL-10R2, glycoprotein 130 (gp130), and IL-13Rα1, to mediate STAT-dependent cytokine signaling.^2,1,3 TYK2 is activated by its phosphorylation, which is induced by ligand-bound cytokine receptors via JAK1 or JAK2-mediated transactivation, and is inhibited by suppressor of cytokine signaling (SOCS) proteins or autoinhibited by the JH2 domain.^3,4 TYK2 has roles in numerous immunological processes, including inflammatory and autoimmune diseases, pathogen defense, and allergy, as well as tumor surveillance and cancer.^1,3 TYK2 containing an isoleucine-to-serine substitution (TYK2^I684S) in the JH2 domain has reduced activity but restores cytokine-induced signaling when expressed in TYK2^-/- U1A cells.⁵ TYK2 SNPs have been identified in patients with acute myeloid leukemia, and TYK2 polymorphisms have been associated with systemic lupus erythematosus (SLE) and multiple sclerosis in humans.¹ Cayman's TYK2 JH2 Domain (human, recombinant; aa 575-869) protein can be used for binding assays.

WARNING This product is not for human or veterinary use.

1. Strobl, B., Stoiber, D., Sexl, V., et al. Tyrosine kinase 2 (TYK2) in cytokine signalling and host immunity. Front. Biosci. (Landmark Ed.) 16(9), 3214-3232 (2011).

2. Garrido-Trigo, A., and Salas, A. Molecular structure and function of janus kinases: Implications for the development of inhibitors. J. Crohns Colitis 14(Suppl 2), S713-S724 (2020).

3. Karjalainen, A., Shoebridge, S., Krunic, M., et al. TYK2 in tumor immunosurveillance. Cancers (Basel) 12(1), 150 (2020).

4. Burke, J.R., Cheng, L., Gillooly, K.M., et al. Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci. Transl. Med. 11(502), eaaw1736 (2019).

5. Li, Z., Gakovic, M., Ragimbeau, J., et al. Two rare disease-associated Tyk2 variants are catalytically impaired but signaling competent. J. Immunol. 190(5), 2335-2344 (2013).