five

IL7 binds IL7R:JAK1

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reactome.org2025-03-25 收录
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Interleukin-7 receptor alpha chain (IL7R) binds interleukin-7 (IL7), forming a stable 1:1 IL7:IL7R complex, with a dissociation constant (Kd) of approximately 200 pM (Goodwin et al. 1990, Park et al. 1990). The full-length Interleukin-7 receptor alpha is a 439-residue single-pass transmembrane glycoprotein consisting of three domains: a 219-residue extracellular domain (ECD), a 25-residue transmembrane domain and a 195-residue cytoplasmic domain. The ECD belongs to the cytokine receptor homology class 1 (CRH1) family, consisting of two fibronectin type III (FNIII) domains with three potential disulfide bonds in the N-terminal FNIII domain and a WSXWS primary sequence motif in the C-terminal domain (Bazan 1990). Recruitment of kinases to the cytoplasmic tail of IL7R is required for signal transduction because the intracellular portion of IL7R does not contain intrinsic tyrosine kinase activity. IL7 interacts directly with the extracellular region of IL7R and this leads to the recruitment of the Cytokine receptor common subunit gamma (IL2RG, Gc) and formation of a receptor complex. IL7 binds glycosylated IL7R 300-fold more tightly than unglycosylated. It is thought that IL7 interacts with both IL7R and IL2RG in the final complex (McElroy et al. 2007).

白细胞介素-7受体α链(IL7R)与白细胞介素-7(IL7)结合,形成稳定的一对一IL7:IL7R复合物,其解离常数(Kd)约为200 pM(Goodwin et al. 1990,Park et al. 1990)。全长白细胞介素-7受体α为含有439个氨基酸的单次穿膜糖蛋白,由三个结构域组成:一个219个氨基酸的细胞外结构域(ECD)、一个25个氨基酸的跨膜结构域和一个195个氨基酸的细胞内结构域。ECD属于细胞因子受体同源类1(CRH1)家族,包括两个纤连蛋白型III(FNIII)结构域,N端FNIII结构域中存在三个潜在的二硫键,以及C端结构域中的WSXWS初级序列基序(Bazan 1990)。由于IL7R的细胞内部分不具有内在酪氨酸激酶活性,因此需要募集激酶至IL7R的细胞内尾部以进行信号转导。IL7直接与IL7R的细胞外区域相互作用,这导致细胞因子受体共有亚基γ(IL2RG,Gc)的募集和受体复合物的形成。与未糖基化的IL7R相比,IL7与糖基化的IL7R的结合强度高300倍。据推测,IL7最终复合物中与IL7R和IL2RG均发生相互作用(McElroy et al. 2007)。
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