Association of Shp2 with Phosphorylated IL-22R1 is Required for Interleukin-22-induced MAP Kinase Activation
Association of Shp2 with Phosphorylated IL-22R1 is Required for Interleukin-22-induced MAP Kinase Activation
复制标题
白细胞介素 22 诱导的 MAP 激酶激活需要 Shp2 与磷酸化 IL-22R1 的结合
DOI:
10.1093/jmcb/mjq017
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发表时间:
2010-08-01
影响因子:
5.5
通讯作者:
Wang, Chuangui
中科院分区:
文献类型:
--
作者:
Meng, Songshu;Gui, Qiu;Wang, Chuangui
Interleukin-22 (IL-22) is a member of the IL-10 family of cytokines produced by activated T cells and is involved in several tissue responses. IL-22 signals through a heterodimeric receptor composed of IL-22 receptor 1 (IL-22R1) and IL-10R2, and the intracellular signaling pathways mediated by IL-22 receptor are not completely known. Here we investigate the effect of Src homology-2 containing protein-tyrosine phosphatase (Shp2) on IL-22 signaling pathway using SW480 colon cancer cells as a model. The results show that IL-22 induces IL-22R1 phosphorylation, and Shp2 is recruited to the tyrosine phosphorylated IL-22R1 upon IL-22 stimulation. Furthermore, Tyr251 and Tyr301 of IL-22R1 are required for Shp2 binding to the IL-22R1. Shp2 binding to IL-22R1 and Shp2 protein tyrosine phosphatase activity are required for activation of MAP kinases and signal transducer and activator of transcription (STAT3) phosphorylation by IL-22. These results reveal a critical role of Shp2 in IL-22 mediated signal transduction pathways.