IL-12R beta 1  (白介素-12 受体 β1)

IL-12 受体是一种 I 型细胞因子受体，与 IL-12结合。主要在 NK 和 T 细胞上表达，由 beta 1和 beta 2 亚基组成，是 gp130 细胞因子受体超家族的成员。IL-12R beta 1 (简称 IL-12R1 或 IL-12Rβ1) 是 IL-12 受体的一个亚基。 IL-12Rβ1，也称为 CD212（分化簇 212），是其人类基因的名称。其编码的蛋白是一种 I 型跨膜蛋白，属于造血素受体超家族。IL-12Rβ1 可以形成二硫键连接的寡聚体，这是与 IL-12 结合活性所必需的，并以低亲和力方式与 IL-12 结合。与此同时，IL-12Rβ1 蛋白可以和 IL-12Rβ2 蛋白共表达，导致高亲和力 IL-12 结合位点的形成和 IL-12 依赖性信号传导的重建^[1]。IL-12 与 IL-12 受体结合后，与 IL-12Rβ1 直接相互作用的细胞质蛋白 TYK2 和与 IL-12Rβ2 相互作用的 JAK2 被酪氨酸磷酸化。磷酸化的 TYK2 和 JAK2 是随后酪氨酸磷酸化和激活与 IL-12Rβ2 结合的 STAT4 所必需的。STAT4 是一种转录因子，随后发生同二聚体化、易位至细胞核并与其靶 DNA 结合以激活 IFN-γ 和其他靶基因的转录。IL-12Rβ1 还与 IL23R 结合形成 IL-23 受体，在 IL-23 信号转导中发挥作用，可能通过激活 Jak-Stat 信号级联。IL-12Rβ1 在淋巴细胞表面以低强度组成型表达，可以通过 T 细胞激活或通过各种白细胞介素 (如 IL-2、IL-7 和 IL-15) 刺激而高度上调。也在树突状细胞上表达。该基因缺乏表达会导致严重分枝杆菌和沙门氏菌感染患者的免疫缺陷^[2]。

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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