JAK3 Kinase Domain (human, recombinant)

JAK3 is a non-receptor tyrosine kinase that has roles in cytokine signaling and immune cell function.^1,2 It is composed of N-terminal FERM and SH2 domains, a regulatory JH2 pseudokinase domain, and a C-terminal kinase domain.^2,3 JAK3 is constitutively expressed in natural killer (NK) cells and thymocytes and expressed upon cell activation in T cells, B cells, and monocytes.⁴ Following cytokine binding to the IL-2 receptor (IL-2R), IL-4R, IL-7R, IL-9R, IL-15R, or IL-21R, JAK3 binds to the γc subunit of the receptor and induces heterodimerization of the receptor subunits and activation of STAT transcription factors.^1,2,4 Through activation of these receptors, JAK3-mediated signaling is involved in T cell proliferation, differentiation, and survival, B cell differentiation and function, and macrophage activation, among other activities.^1,2 Loss-of-function mutations in JAK3 are associated with autosomal recessive severe combined immunodeficiency disease (SCID), while gain-of-function mutations are associated with immune dysregulation and blood cancers, including myeloproliferative neoplasms, T cell lymphomas and leukemias, NK lymphoma-leukemia, and acute lymphoblastic leukemia.^2,5,6 Cayman's JAK3 Kinase Domain (human, recombinant) protein can be used for enzyme activity assays. This protein has a calculated molecular weight of 37 kDa.

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1. Benczik, M., and Gaffen, S.L. The interleukin (IL)-2 family cytokines: Survival and proliferation signaling pathways in T lymphocytes. Immunol. Invest. 33(2), 109-142 (2004).

2. Liongue, C., Ratnayake, T., Basheer, F., et al. Janus kinase 3 (JAK3): A critical conserved node in immunity disrupted in immune cell cancer and immunodeficiency. Int. J. Mol. Sci. 25(5), 2977 (2024).

3. Leonard, W.J., and O'Shea, J.J. Jaks and STATs: Biological implications. Annu. Rev. Immunol. 16, 293-322 (1998).

4. Notarangelo, L.D., and Candotti, F. JAK3-deficient severe combined immunodeficiency. Radiol. Clin. North Am. 20(1), 97-111 (2000).

5. Ott, N., Faletti, L., Heeg, M., et al. JAKs and STATs from a clinical perspective: Loss-of-function mutations, gain-of-function mutations, and their multidimensional consequences. J. Clin. Immunol. 43(6), 1326-1359 (2023).

6. Philips, R.L., Wang, Y., Cheon, H., et al. The JAK-STAT pathway at 30: Much learned, much more to do. Cell 185(21), 3857-3876 (2022).