IL-12R beta 1

The IL-12 receptor is a type I cytokine receptor that binds to IL-12. It is expressed primarily on NK and T cells and consists of beta 1 and beta 2 subunits and is a member of the gp130 cytokine receptor superfamily. IL-12R beta 1 (abbreviated IL-12R1 or IL-12Rβ1) is a subunit of the IL-12 receptor. IL-12R beta 1, also known as CD212 (cluster of differentiation 212), is the name of its human gene. It encodes a type I transmembrane protein belonging to the hematopoietin receptor superfamily. IL-12Rβ1 can form disulfide-linked oligomers, which are required for IL-12 binding activity, and binds to IL-12 with low affinity. In parallel, IL-12Rβ1 protein can be co-expressed with IL-12Rβ2 protein, leading to the formation of high-affinity IL-12 binding sites and the reconstitution of IL-12-dependent signaling^[1].
Upon IL-12 binding to the IL-12 receptor, the cytoplasmic protein TYK2, which interacts directly with IL-12Rβ1, and JAK2, which interacts with IL-12Rβ2, are tyrosine phosphorylated. Phosphorylated TYK2 and JAK2 are required for subsequent tyrosine phosphorylation and activation of STAT4, which binds to IL-12Rβ2. STAT4 is a transcription factor that subsequently homodimerizes, translocates to the nucleus and binds to its target DNA to activate transcription of IFN-γ and other target genes. IL-12Rβ1 also binds to IL23R to form the IL-23 receptor, which is involved in IL-23 signaling. It plays a role in IL-23 signaling, possibly through activation of the Jak-Stat signaling cascade. IL-12Rβ1 is expressed in a low intensity constitutive phenotype on the surface of lymphocytes and can be highly upregulated by T cell activation or by stimulation with various interleukins such as IL-2, IL-7 and IL-15. It is also expressed on dendritic cells. Lack of expression of this gene leads to immunodeficiency in patients with severe Mycobacterium and Salmonella infections^[2].

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