Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
Biochem Biophys Res Commun. 2010 Feb 5;392(2):171-7. doi: 10.1016/j.bbrc.2010.01.004. Epub 2010 Jan 6.
Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates T-cell, B-cell, NK-cell, and myeloid-cell functions. IL-21 binds with its cognate receptor complex, which consists of the IL-21 receptor (IL-21R) and the common gamma chain (gammac) receptor subunit. We identified novel IL-21R-binding molecule, WD-40 repeats containing SOCS-box-2, WSB-2. WSB-2 associated with the membrane-proximal intracytoplasmic region of IL-21R, including box1 and box2. Overexpression study of WSB-2 showed the reduction of IL-21R expression and IL-21-induced signal transduction. On the other hand, small interfering RNA for WSB-2 enhanced the expression level of IL-21R and IL-21-induced STAT3 activation, indicating that WSB-2 negatively controls the receptor expression. This report provides the first evidence that WSB-2 is a regulator of IL-21R expression and IL-21-induced signal transduction.
白细胞介素-21（IL-21）是一种多效细胞因子，调节 T 细胞、B 细胞、NK 细胞和髓系细胞的功能。IL-21 与其同源受体复合物结合，该复合物由 IL-21 受体（IL-21R）和共同γ链（gammac）受体亚基组成。我们鉴定了新的 IL-21R 结合分子，含 WD-40 重复序列的 SOCS 框-2（WSB-2）。WSB-2 与 IL-21R 的膜近端胞质内区域相关，包括框 1 和框 2。WSB-2 的过表达研究表明，IL-21R 表达和 IL-21 诱导的信号转导减少。另一方面，WSB-2 的小干扰 RNA 增强了 IL-21R 的表达水平和 IL-21 诱导的 STAT3 激活，表明 WSB-2 负调控受体表达。本报告首次证明 WSB-2 是 IL-21R 表达和 IL-21 诱导的信号转导的调节剂。
