Wei Sherry H-Y, Ming-Lum Andrew, Liu Ying, Wallach David, Ong Christopher J, Chung Stephen W, Moore Kevin W, Mui Alice L-F
DNAX Research Institute, Palo Alto, CA 94304, USA.
J Interferon Cytokine Res. 2006 May;26(5):281-90. doi: 10.1089/jir.2006.26.281.
The cytokine interleukin-10 (IL-10) is an important regulator of immune cell function, proliferation, and survival. The IL-10 receptor (IL-10R) consists of two subunits, IL-10R1 and IL-10R2, both belonging to the class II cytokine receptor superfamily. Like other members of the cytokine receptor superfamily, IL-10R stimulation leads to activation of Jak family kinases and Stat transcription factors. To identify additional signal transduction pathways used by the IL-10R, we purified 92-kDa and 100-kDa proteins that coprecipitated with IL-10R1 from IL-10-stimulated cells. Both proteins were found to be related to the 97-kDa subunit of the regulatory component of the 26S proteasome. Subsequent studies confirmed that the IL-10R1 undergoes ligand- dependent internalization and proteasome-mediated degradation. An IL-10R1 cytoplasmic domain mutant deficient for internalization exhibited prolonged signaling through Jak1 and Stat3, reinforcing the importance of receptor internalization for signal termination.
细胞因子白细胞介素-10（IL-10）是免疫细胞功能、增殖和存活的重要调节因子。IL-10受体（IL-10R）由两个亚基组成，即IL-10R1和IL-10R2，二者均属于II类细胞因子受体超家族。与细胞因子受体超家族的其他成员一样，IL-10R的刺激会导致Jak家族激酶和Stat转录因子的激活。为了确定IL-10R所使用的其他信号转导途径，我们从IL-10刺激的细胞中纯化了与IL-10R1共沉淀的92 kDa和100 kDa蛋白。发现这两种蛋白均与26S蛋白酶体调节成分的97 kDa亚基相关。随后的研究证实，IL-10R1会发生依赖配体的内化和蛋白酶体介导的降解。缺乏内化功能的IL-10R1胞质结构域突变体通过Jak1和Stat3表现出延长的信号传导，这进一步证明了受体内化对于信号终止的重要性。
