期刊文献+

FGF受体-1和FGF受体-2介导成纤维细胞生长因子-21信号传导 被引量:2

原文传递
导出
摘要 成纤维细胞生长因子-21是FGF家族成员,FGF-21与其他FGF家族成员不同,它没有促进细胞分裂的作用,但具有很强的调节血糖作用.本实验旨在系统研究FGF-21的功能受体,以及配体/受体的作用机制,为深入研究FGF-21的生物功能,加快FGF-21从基因到药物的转变奠定理论基础.前期实验表明,FGF-21促进3T3-L1脂肪细胞葡萄糖代谢,对前脂肪细胞无作用,说明3T3-L1脂肪细胞表达FGF-21功能受体.本文以3T3-L1脂肪细胞为靶标,深入研究FGF-21的功能受体.在FGF-21作用下3T3-L1脂肪细胞中的FGF受体1(R1)和FGF受体2(R2)形成特异性异源二聚体.脂肪细胞经FGF-21处理后,R1和R2均迅速发生磷酸化,表明两个受体均被FGF-21激活.siRNA干涉实验表明,抑制R1和R2功能可以抑制FGF-21处理后3T3-L1脂肪细胞Glut1的表达水平,揭示了FGF-21通过R1和R2上调3T3-L1脂肪细胞中Glut1的表达.免疫印迹结果表明,FGF-21可以介导3T3-L1脂肪细胞表面R1和R2的内吞.克隆后测序分析结果表明,3T3-L1脂肪细胞表达的FGF受体为FGFR-1Ⅲc和FGFR-2Ⅲc.结果表明,FGFR-1Ⅲc和FGFR-2Ⅲc是FGF-21的功能受体,参与FGF-21在脂肪细胞中介导的糖代谢活性的信号传导.
出处 《中国科学:生命科学》 CSCD 北大核心 2010年第4期332-341,共10页 Scientia Sinica(Vitae)
基金 黑龙江省科技厅重点攻关项目(批准号:2006G0461-00)资助
  • 相关文献

参考文献21

  • 1Powers C J, McLeskey S W, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endocrine-Related Cancer, 2000, 7: 165-- 197.
  • 2Eswarakumar V P, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev, 2005, 16: 139--149.
  • 3Yamashita T, Yoshioka M, Itoh N. Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. Biochem Biophys Res Commol/Lun, 2000, 277:494--498.
  • 4Yeh B K, Igarashi M, Eliseenkova A V, et al. Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. Proc Natl Acad Sci USA, 2003, 100:2266--2271.
  • 5Olsen S K, Ibrahimi O A, Raucci A, et al. Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity. Proc Natl Acad Sci USA, 2004, 101 : 935--940.
  • 6Pellegrini L, Burke D F, von Delft F, et al. Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin. Nature, 2000, 407:1029--1034.
  • 7Plotnikov A N, Schlessinger J, Hubbard S R, et al. Structural basis for FGF receptor dimerization and activation. Cell, 1999, 98:641--650.
  • 8Bellot F, CrumLey G, Kaplow J M, et al. Ligand-induced transphosphorylation between different FGF receptors. EMBO, 1991, 10: 2849-- 2854.
  • 9Schlessinger J, Plotnikov A N, Ibrahimi O A, et al. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Molecular cell, 2000, 6:743--750.
  • 10Xie M H, Holcomb I, Deuel B, et al. FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4. Cytokine, 1999, 11: 729--735.

二级参考文献69

  • 1张崇本,张晓兰,李成健,成俊英,吴显荣.小鼠3T3-L1前脂肪细胞系的特异性标记(英文)[J].中国生物化学与分子生物学报,2004,20(5):583-586. 被引量:2
  • 2李江红,张宗玉,童坦君.肽类生长因子对抗癌基因的诱导作用[J].生物化学杂志,1994,10(5):626-629. 被引量:1
  • 3Mohammadi M, Olsen S K, Ibrahimi O A. Structural basis for fibroblast growth factor receptor activation[J]. Cytokine Growth Factor Rev, 2005,16 (2): 107-137
  • 4Nishimura T, Nakatake Y, Konishi M, et al. Identification of a novel FGF, FGF-21, preferentially expressed in the liver [J]. Biochim Biophys Acta, 2000, 1492( 1 ) : 203-206
  • 5Kharitonenkov A, Shiyanova T L, Koester A, et al. FGF-21 as a novel metabolic regulator[J]. J Clin Invest, 2005, 115(6) : 1627- 1635
  • 6Wente W, Efanov A M, Brenner M, et al. Fibroblast growth factor- 21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways [J]. Diabetes, 2006, 55(9): 2470-2478
  • 7Kharitonenkov A, Wroblewski V J, Koester A, et al. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21 [J]. Endocrinology, 2007, 148(2): 774-781
  • 8Mohammadi M, McMahon G, Sun L, et al. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors[ J]. Science, 276(5314) : 955-960
  • 9Huang X, Yu C, Jin C, et al. Forced expression of hepatocytespecific fibroblast growth factor 21 delays initiation of chemically induced hepatocarcinogenesis [ J ]. Mol Carcinog, 2006, 45 ( 12 ) : 934-942
  • 10Powers C J, McLeskey S W, Wellstein A. Fibroblast growth factors, their receptors and signaling[J]. Endocr Relat Cancer, 2000, 7(3) : 165-197

共引文献22

同被引文献20

  • 1Haslam D W, James W P. Obesity [J]. Lancet, 2005, 366(9492) : 1197 - 1209.
  • 2Lundasen T, Hunt M C, Nilsson L M, et al. PPAH.alpha is a key regu- lator of hepatic FGF21 [J]. Biochem Biophys Res Commun, 2007, 360 ( 2 ) : 437 - 440.
  • 3Zhang X, Yeung D C, Karpisek M, et al. Serum FGF21 levels are in- creased in obesity and are independently associated with the metabolic syndrome in humans [ J ]. Diabetes, 2008, 57 (5) : 1246 - 12.53.
  • 4Coskun T, Bina H A, Schneider M A, et al. Fibroblast growth factor 21 corrects obesity in mice [ J ]. Endocrinology, 2008, 149 (12) : 6018 - 6027.
  • 5Xu J, Lloyd 1) J, Hale C, et al. Fibroblast growth factor 21 reverses hepatic steatosis, inereases energy: expenditure, and improves insulin sensitivity in diet-induced obese mice [ J ]. Diabetes, 2009, 58 ( 1 ) : 250 - 259.
  • 6Zhang Y, Edwards P A. FXR signaling in metabolic disease [ J ]. FEBS Lett, 2008, 582(1) : 10 - 18.
  • 7王永超,刘红,彭家和,等.法尼酯X受体上调肝细胞中成纤维细胞生长因子21的表达[J].第i军医大学学报,2011,33(9):912-915.
  • 8Kharitonenkov A, Shiyanova T L, Koester A, et al. FGF-21 as a novel metabolic regulator [J]. J Clin invest, 2005, 115(6) : 1627 - 1635.
  • 9Moyers J S, Shiyanova T L, Mehrbod F, et al. Molecular determi- nants of FGF-21 activity-synergy and cross-talk with PPARgamma sig- naling [J]. J Cell Physiol, 2007. 210(1): 1 -6.
  • 10Badman M K, Koester A, Flier J S, et al. Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis[ J]. En- docrinology, 2009, 150( 11 ) : 4931 -4940.

引证文献2

二级引证文献5

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