期刊文献+

G蛋白偶联受体激酶5在有丝分裂中的作用 被引量:2

The Role of GRK5 in Mitosis
原文传递
导出
摘要 G蛋白偶联受体激酶(GRK)是G蛋白偶联受体(GPCR)信号通路的负性调节因子。近来的研究发现,GRK除了磷酸化G蛋白偶联受体使其脱敏外,还能与其他非受体底物结合,功能呈现多样性。GRK5是GRK家族成员之一,该研究探索了GRK5在细胞周期和有丝分裂中的作用,结果显示:在细胞内干扰GRK5的表达导致分裂中期的细胞数目增多和细胞凋亡。进一步的研究发现,干扰GRK5的表达导致有丝分裂中期的染色体不能正常排列到赤道板,而对分裂后期染色质分离以及胞质分裂没有影响。在细胞内干扰GRK蛋白家族的另一个成员GRK2对有丝分裂则没有明显影响。该研究提示GRK5是细胞有丝分裂的重要调控蛋白。 G protein-coupled receptor(GPCR) kinases(GRKs) are known as a family of serine/threonine kinases that desensitize GPCR signaling by phosphorylating agonist-occupied receptors.Receptor phosphorylation catalyzed by GRK leads to the recruitment of arrestins to the cell membrane and the internalization of GPCRs.GRKs are also capable to phosphorylate a variety of non-GPCR substrates and regulate several signaling pathways via direct interactions with other proteins in a phosphorylation-independent manner.GRK5 is an important member of GRKs.The current study explored potential roles of GRK5 in cell cycle and cell mitosis.Our results showed that knockdown of GRK5 arrests cells in metaphase and induces cell apoptosis.Using DAPI labeling chromosome,we found that knockdown of GRK5 induces chromosome misalignment but has no effect on cytokinesis.However,knockdown of GRK2,another member of GRKs,has no effect on cell cycle and cell mitosis.Our results suggest that GRK5 is an important regulator of cell mitosis.
出处 《中国细胞生物学学报》 CAS CSCD 北大核心 2012年第3期234-239,共6页 Chinese Journal of Cell Biology
基金 国家自然科学基金(No.30900852 No.30900438)资助项目~~
关键词 G蛋白偶联受体激酶 有丝分裂 细胞凋亡 细胞周期 G protein-coupled receptor kinase mitosis apoptosis cell cycle
  • 相关文献

参考文献34

  • 1Pitcher JA,Freedman NJ,Lefkowitz RJ.G protein-coupled re-ceptor kinases.Annu Rev Biochem 1998;67:653-92.
  • 2Guo J,Wu Y,Zhang W,Zhao J,Devi LA,Pei G,et al.Identifica-tion of G protein-coupled receptor kinase 2 phosphorylation sitesresponsible for agonist-stimulated delta-opioid receptor phospho-rylation.Mol Pharmacol 2000;58(5):1050-.
  • 3Martini JS,Raake P,Vinge LE,DeGeorge BR Jr,ChuprunJK,Harris DM,et al.Uncovering G protein-coupled receptorkinase-5 as a histone deacetylase kinase in the nucleus of cardio-myocytes.Proc Natl Acad Sci USA 2008;105(34):12457-62.
  • 4Eckhart AD,Duncan SJ,Penn RB,Benovic JL,Lefkowitz RJ,Koch WJ.Hybrid transgenic mice reveal in vivo specificity ofG protein-coupled receptor kinases in the heart.Circ Res 2000;86(1):43-50.
  • 5Sorriento D,Ciccarelli M,Santulli G,Campanile A,AltobelliGG,Cimini V,et al.The G-protein-coupled receptor kinase 5inhibits NFkappaB transcriptional activity by inducing nuclearaccumulation of IkappaB alpha.Proc Natl Acad Sci US.
  • 6Freeman JL,de la Cruz EM,Pollard TD,Lefkowitz RJ,PitcgerJA.Regulation of G protein-coupled receptor kinase 5(GRK5)by actin.J Biol Chem 1998;273(32):20653-7.
  • 7Johnson LR,Scott MG,Pitcher JA.G protein-coupled receptorkinase 5 contains a DNA-binding nuclear localization sequence.Mol Cell Biol 2004;24(23):10169-79.
  • 8Chen YJ,Wang FF,Long H,Chen Y,Wu ZY,Ma L.GRK5promotes F-actin bundling and targets bundles to membranestructures to control neuronal morphogenesis.J Cell Biol 2011;194(6):905-20.
  • 9Cimini D,Degrassi F.Aneuploidy:A matter of bad connections.Trends Cell Biol 2005;15(8):442-51.
  • 10Hassold T,Hunt P.To err(meiotically)is human:The genesis ofhuman aneuploidy.Nat Rev Genet 2001;2(4):280-91.

同被引文献13

引证文献2

二级引证文献2

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