期刊文献+

小鼠免疫抑制蛋白SOCS3脯氨酸富集区为其生物学功能所必需 被引量:2

Proline-rich Region in Immune Suppression Protein SOCS3 is Required for Its Biological Functions
下载PDF
导出
摘要 SOCS3(suppressors of cytokine signaling 3)可以调节信号转导过程并影响造血干细胞的分化.利用生物信息学方法,发现SOCS3蛋白含有脯氨酸富集区,采用重组PCR技术缺失SOCS3蛋白中的129-161位的氨基酸(SOCS3Δ129-161),并将其克隆到pcDNA31/V5质粒载体中.转染细胞,然后通过流式细胞技术,分析预测的功能区对SOCS3蛋白功能的影响.结果表明,此脯氨酸富集区对SOCS3蛋白的三级结构和功能有重要的意义.建模结果显示,SOCS3Δ129-161蛋白结构发生显著变化.脯氨酸富集区的缺失也影响小鼠骨髓细胞向CD8^+T细胞分化.研究结果显示,SOCS3蛋白中129-161位的脯氨酸富集区在其结构和功能上有重要的作用. Suppressor of cytokine signaling 3 (SOCS3) negatively regulates signal transduction and exerts an important role in regulating the differentiation of hematopoietic cells. SOCS3 contains an proline-rich region as determined by bioinformatics-based analysis. To determine the role of this proline-rich region, the deletion mutant of SOCS3 amino acids 129- 161 (SOCS3△129-161) was obtainde using PCR and then cloned into pcDNA31/V5 recombinant plasmid. The functions of SOCS3△129-161were analyzed by flow cytometry in transfected cells. The results showed that the three-dimensional structure of SOCS3△129-161 was clearly different from that of wildtype as predicted by comparative(homology) computation modeling. In addition, the SOCS3△129-161 abrogated the functions of native SOCS3, inducing CD8^+ T cell differentiation. The results suggested that the proline-rich region within amino acids 129 - 161 of SOCS3 might play an important role in the formation and maintaining of SOCS3 tertiary structure and significantly contributed for its biological functions.
机构地区 南开大学医学院
出处 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2008年第5期432-438,共7页 Chinese Journal of Biochemistry and Molecular Biology
基金 国家自然科学基金(No.30540022) 国家科技部基金(No.06C26211200695) 国家高技术研究发展计划(863计划 No.2006AA020502) 天津市科委基金(No.07JCZDJC03300 06ZHCXSH04800)~~
关键词 SOCS3 蛋白三级结构建模 重组PCR 流式分析 SOCS3 tertiary structure modeling recombinant PCR FACS
  • 相关文献

参考文献19

  • 1Krebs D L, Hilton D J. SOCS Proteins: Negative Regulators of Cytokine Signaling [J]. Stem Cells, 2001, 19(5) :378-387
  • 2Ilangumaran S, Ramanathan S, Rottapel R Regulation of the immune system by SOCS family adaptor proteins[J]. Semin Immunol, 2004, 16(6) :351-365
  • 3Fujimoto M, Naka T. Regulation of cytokine signaling by SOCS family molecules[J]. Trends Immunol,2003, 24(12) : 659-666
  • 4Yoshimura A, Nishinakamura H, Matsumura Y, et al. Negative regulation of cytokine signaling and immune responses by SOCS proteins[J]. Arthritis Res Ther, 2005, 7(3) : 100-110
  • 5Trop S, De Sepulveda P, Zuniga-Pfiucker J C, et al. Overexpression of suppressor of cytokine signaling-1 impairspre-T-cell receptor- induced proliferation but not differentiation of immature thymocytes [J]. Blood, 2001,97(8): 2269-2277
  • 6Yasukawa H, Ohishi M, Mori H, et al. IL-6 induces an antiinflammatory response in the absence of SOCS3 in macrophages [ J ]. Nat Immunol, 2003, 4(6) : 551-556
  • 7Lang R, Pauleau A L, Parganas E, et al. SOCS3 regulates the plasticity of gp130 signaling[ J ]. Nat Immunol, 2003, 4 (6) : 546-550
  • 8Croker B A, Croker B A, Krebs D L, et al. SOCS3 negatively regulates IL-6 signaling in vivo[J]. Nat Immunol, 2003, 4(6):540- 545
  • 9Kimura A, Kinjyo I, Matsumura Y, et al. SOCS3 is a. physiological negative regulator for granulopoiesis and granulocyte colonystimulating factor receptor signaling [ J ]. J Biol Chem, 2004, 279 (8) :6905-6910
  • 10Croker B A, Metcalf D, Robb L, et al. SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis[ J]. Immunity, 2004, 20(2) : 153-165

二级参考文献14

  • 1Spiegelman B M, Flier J S. Obesity and the regulation of energy balance[J]. Cell, 2001,104(4) :531-543
  • 2Dotsch J, Rascher W, Meissner U. New insights into leptin resistance by modifying cytokine receptor signal transduction [ J ]. Eur J Endoerinol, 2005,152(3) :333-334
  • 3Starr R, Willson T A, Viney E M, et al. A family of cytokine-inducible inhibitor's of signalling[J]. Nature, 1997,387(6636) :917-921
  • 4Wang Z, Zhou Y T, Kakuma T, et al. Leptin resistance of adipocytes in obesity: role of suppressors of cytokine signaling [ J ].Biochem Biophys Res Commun, 2000,277( 1 ) : 20-26
  • 5Bjorbaek C, El-Haschimi K, Frantz JD, et al. The role of SOCS-3 in leptin signaling and leptin resistance[J]. J Biol Chem, 1999,274(42) : 30059-30065
  • 6Krebs D L, Hilton D J. SOCS proteins: negative regulators of cytokine signaling[J]. Stem Cells, 2001,19(5) :378-387
  • 7Wormald S, Zhang J G, Krebs D L, et al. The comparative roles of suppressor of cytokine signaling-1 and -3 in the inhibition and desensitization of cytokine signaling [ J ]. J Biol Chem, 2006, 281(16):11135-11143
  • 8Takahashi Y, Carpino N, Cross J C, et al. SOCS3 : an essential regulator of LIF receptor signaling in trophoblast giant cell differentiation[J]. EMBO J, 2003,22(3) :372-384
  • 9Larseu L, Ropke C. Suppressors of cytokine signalling: SOCS[J].APMIS, 2002, 110( 12 ) : 833-844
  • 10Hood R L, Allen C E, Cellularity of bovine adipose tissue[J]. J Lipid Res, 1973,14(6) :605-610

共引文献7

同被引文献69

  • 1张莉红,徐永健,张珍祥.SOCS在哮喘发病中的作用[J].国外医学(呼吸系统分册),2005,25(9):663-664. 被引量:1
  • 2王念鸿,郭晓蕙.SOCS-3与胰岛素抵抗[J].国外医学(内分泌学分册),2005,25(6):409-411. 被引量:5
  • 3邹大进,吴鸿.腹型肥胖致胰岛素抵抗的机制及治疗展望[J].中国糖尿病杂志,2006,14(4):309-312. 被引量:39
  • 4Hopkins A L, Groom C R. The druggable genome[J] . Nat Rev Drug Discov, 2002, 1(9) : 727-730
  • 5Seed B, Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythroeyte receptor, by a rapid immunoselection procedure[J] .Proc Natl Acad Sci U S A, 1987, 84(10) : 3365-3369
  • 6Yamasaki K, Taga T, Hirata Y, et al. Cloning and expression of the human interleukin-6 ( BSF-2/IFN beta 2 ) receptor [ J ]. Science, 1988, 241(4867): 825-828
  • 7Kitamura T. New experimental approaches in retrovirus-mediated expression screening[J]. Int J Hematol, 1998, 67(4) :351-359
  • 8Zannettino A C, Rayner J R, Ashman L K, et al. A powerful new technique for isolating genes encoding cell surface antigens using retroviral expression cloning [ J ]. J Immunol, 1996, 156 (2) : 611-620
  • 9Rayner J R, Gonda T J. A simple and efficient procedure for generating stable expression libraries by cDNA cloning in a retroviral vector[J] .Mol Cell Biol, 1994, 14(2): 880-887
  • 10Wong B Y, Chen H, Chung S W, et al. High-efficiency identification of genes by functional analysis from a retroviral cDNA expression library[J] .J Viral, 1994, 68(9) : 5523-5531

引证文献2

二级引证文献15

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部