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SH-2-containing protein tyro-sine phosphatase 1 is required for IL-4-induced IL-4R expression in spleen cells

Science b.lletin 2005年第14期 50-55页

作者： CAO Xin1, HUANG Zan2 & FAN Jingyi3 1. Department of Cell b.ology and Medical Genetics, Nanjing Medical University, Nanjing 210029, China 2. Molecular b.ology Program, Stritch School of Medicine, Loyola Uni- versity at Chicago. Maywood, IL 60153, USA 3. Department of Organismal b.ology and Anatomy, University of Chi- cago. Chicago. IL 60637, USA

To investigate the role of SH-2-containing pro- tein tyrosine phosphatase 1, SHP-1, in IL-4-induced IL-4 receptor (IL-4R) expression, we examined IL-4 receptor α-chain (IL-4Rα) mRNA expression in Na3VO4-treated wild type (WT) spleen cells and measured IL-4R mRNA in IL-4-stimulated spleen cells of viab.e motheaten mice (mev/mev). It is found that IL-4-induced IL-4R mRNA ex- pression was impaired in Na3VO4-treated WT spleen cells and IL-4-stimulated mev/mev spleen cells. Here we show that the impaired IL-4-induced IL-4Rα mRNA expression was due to reduced expression of IL-4R that led to impaired STAT6 signaling. We further demonstrate that reduction of IL-4Rα protein expression in mev/mev spleen cells was due to alteration in cell compositions. In mev/mev spleen, the per- centages of CD4+, CD8+, and CD19+ cells expressing rela- tively high levels of IL-4R were reduced dramatically while the percentages of Mac-1+ and Gr-1+ cells with relative low levels of IL-4R increased greatly. Despite the profound effect of reduced expression of IL-4R protein, the IL-4Rα mRNA expression was comparab.e in spleen cells of littermate con- trol mice (+/?) and mev/mev mice and no differences were found in b.cells, T cells, and macrophages, suggesting cell type-specific downregulation of IL-4R expression in macro- phages through a posttranscriptional mechanism. Our study suggests that SHP-1 is required for IL-4-meidated function and indirectly regulates IL-4-meidated function in spleen cells b. affecting hematopoiesis.

关键词： SHP-1 IL-4 receptor STAT6 signaling viab.e mot- heaten.

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