PI3K/Akt信号通路相关的生物学调控机制研究进展
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摘要
PI3K/Akt信号通路是由酶联受体介导的信号转导通路,该通路不仅参与多种生长因子、细胞因子和细胞外基质等的信号转导,同时还参与细胞增殖、分化、凋亡和葡萄糖转运等多种细胞功能的调节,特别是在细胞凋亡、细胞存活以及调控细胞糖代谢等方面具有重要作用。本研究综述了PI3K-Akt信号通路的结构组成、通路活化、通信过程、调控机制及其生物学功能等方面的研究进展,为进一步研究PI3K/Akt信号通路的生物学调控作用机制提供启示。
PI3K/Akt signal pathway is a signal transduction pathway mediated by enzyme-linked receptor, which not only participates in signal transduction of various growth factors, cytokines and extracellular matrix, but also participates in the regulation of cell proliferation, differentiation, apoptosis, glucose transport and other cell functions.In particular, it plays an important role in cell apoptosis, cell survival, and regulation of cell sugar metabolism. This paper reviewed the research progress of PI3K/Akt signal pathway on the structure composition, pathway activation,communication process, regulatory mechanism and biological function, and provided suggestions for the further study on the mechanism of biological regulation of PI3K/Akt signaling pathway.
PI3K/Akt signal pathway is a signal transduction pathway mediated by enzyme-linked receptor, which not only participates in signal transduction of various growth factors, cytokines and extracellular matrix, but also participates in the regulation of cell proliferation, differentiation, apoptosis, glucose transport and other cell functions.In particular, it plays an important role in cell apoptosis, cell survival, and regulation of cell sugar metabolism. This paper reviewed the research progress of PI3K/Akt signal pathway on the structure composition, pathway activation,communication process, regulatory mechanism and biological function, and provided suggestions for the further study on the mechanism of biological regulation of PI3K/Akt signaling pathway.
引文
Boland E.,Clayton-Smith J.,Woo V.G.,McKee S.,Manson F.D.C.,Medne L.,Zackai E.,Swanson E.A.,Fitzpatrick D.,Millen K.J.,Sherr E.H.,Dobyns W.B.,and Black G.C.,2007,Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum,Am.J.Hum.Genet.,81(2):292-303
Chen Y.L.,Law P.Y.,and Loh H.H.,2008,NGF/PI3K signaling-mediated epigenetic regulation of delta opioid receptor gene expression,Biochem.Biophys.Res.Commun.,368(3):755-760
Cleasby M.E.,Reinten T.A.,Cooney G.J.,James D.E.,and Kraegen E.W.,2007,Functional studies of Akt isoform specificity in skeletal muscle in vivo;maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression,Mol.Endocrinol.,21(1):215-228
Deng D.J.,2014,DNA methylation and demethylation:current status and future perspective,Yichuan(Hereditas),36(5):403-410(邓大君,2014,DNA甲基化和去甲基化的研究现状及思考,遗传),36(5):403-410)
Egerman M.A.,and Glass D.J.,2014,Signaling pathways controlling skeletal muscle mass,Crit.Rev.Biochem.Mol.Biol.,49(1):59-68
Hou W.Y.,Zhang Y.S.,Niu H.F.,and Xin Y.P.,2013,Epigenetic regulation of Akt gene on muscle cell development,Jiachu Shengtai Xuebao(Acta Ecologiae Animalis Domastici),34(4):6-9(侯伟媛,张云生,牛华锋,辛亚平,2013,Akt基因对肌肉细胞发育的表观调控,家畜生态学报,34(4):6-9)
Huang Y.Z.,Li M.X.,Wang J.,Zhan Z.Y.,Sun Y.J.,Sun J.J.,Li C.J.,Lan X.Y.,Lei C.Z.,Zhang C.L.,and Chen H.,2013,A5'-regulatory region and two coding region polymorphisms modulate promoter activity and gene expression of the growth suppressor gene ZBED6 in cattle,PLoS One,8(11):e79744
Huang Y.Z.,Sun J.J.,Zhang L.Z.,Li C.J.,Womack J.E.,Li Z.J.,Lan X.Y.,Lei C.Z.,Zhang C.L.,Zhao X.,and Chen H.,2014,Genome-wide DNA methylation profiles and their relationships with m RNA and the microRNA transcriptome in bovine muscle tissue(Bos taurine),Scientific Reports,4:6546
Ji M.,Zhang Q.,Ye J.W.,Wang X.Y.,Yang W.,and Zhu D.H.,2008,Myostatin induces p300 degradation to silence cyclin D1 expression through the PI3K/PTEN/Akt pathway,Cell Signal,20(8):1452-1458
Li Jing,Zhang Y.S.,Li N.,Hu X.X.,Shi G.Q.,Liu S.R.,and Liu N.,2013,Expression of Myogenin and MCK genes regulated by PI3K/AKT pathway,Yichuan(Hereditas),35(5):637-642(李晶,张云生,李宁,胡晓湘,石国庆,刘守仁,柳楠,2013,PI3K/AKT信号通路调控Myogenin和MCK基因的表达,遗传,35(5):637-642)
Li Z.B.,Kollias H.D.,and Wagner K.R.,2008,Myostatin directly regulates skeletal muscle fibrosis,J.Biol.Chem.,283(28):19371-19378
Obrochta K.M.,Krois C.R.,Campos B.,and Napoli J.L.,2015,Insulin regulates retinol dehydrogenase expression and alltrans-retinoic acid biosynthesis through Fox O1,J.Biol.Chem.,290(11):7259-7268
Orlando D.A.,Chen M.W.,Brown V.E.,Solanki S.,Choi Y.J.,Olson E.R.,Fritz C.C.,Bradner J.E.,and Guenther M.G.,2014,Quantitative ChIP-Seq normalization reveals global modulation of the epigenome,Cell Rep.,9(3):1163-1170
Pansters N.A.,Schols A.M.,Verhees K.J.,de Theije C.C.,Snepvangers F.J.,Kelders M.C.,Ubags N.D.,Haegens A.,and Langen R.C.,2015,Muscle-specific GSK-3βablation accelerates regeneration of disuse-atrophied skeletal muscle,Biochim.Biophys.Acta,Mar.,1852(3):490-506
Serra C.,Palacios D.,Mozzetta C.,Forcales S.V.,Morantte I.,Ripani M.,Jones D.R.,Du K.Y.,Jhala U.S.,Simone C.,and Puri P.L.,2007,Functional interdependence at the chromatin level between the MKK6/p38 and IGF1/PI3K/AKT pathways during muscle differentiation,Mol.Cell,28(2):200-213
Shi J.,Luo L.Q.,Eash J.,Ibebunjo C.,and Glass D.J.,2011,The SCF-Fbxo40 complex induces IRS1 ubiquitination in skeletal muscle,limiting IGF1 signaling,Dev.Cell,21(5):835-847
Song B.Y.,and Zhu W.G.,2011,Advances in effector protein of histone methylation,Yichuan(Hereditas),33(4):285-292(宋博研,朱卫国,2011,组蛋白甲基化修饰效应分子的研究进展,遗传,33(4):285-292)
Wang R.X.,and Xu J.H.,2014,Genomic DNA methylation and histone methylation,Yichuan(Hereditas),36(3):191-199(王瑞娴,徐建红,2014,基因组DNA甲基化及组蛋白甲基化,遗传,36(3):191-199)
Ye Y.,Jin L.,Wilmott J.S.,Hu W.L.,Yosufi B.,Thorne R.F.,Liu T.,Rizos H.,Yan X.G.,Dong L.,Tay K.H.,Tseng H.Y.,Guo S.T.,de Bock C.E.,Jiang C.C.,Wang C.Y.,Wu M.,Zhang L.J.,Hersey P.,Scolyer R.A.,and Zhang X.D.,2013,PⅠ(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma,Nat.Commun.,4:1508
Zeng T.,Zhang C.L.,Song F.Y.,Zhao X.L.,and Xie K.Q.,2014,CM Z reversed chronic ethanol-induced disturbance of PPAR-αpossibly by suppressing oxidative stress and PGC-1αacetylation,and activating the MAPK and GSK3βpathway,PLoSOne,9(6):e98658
Chen Y.L.,Law P.Y.,and Loh H.H.,2008,NGF/PI3K signaling-mediated epigenetic regulation of delta opioid receptor gene expression,Biochem.Biophys.Res.Commun.,368(3):755-760
Cleasby M.E.,Reinten T.A.,Cooney G.J.,James D.E.,and Kraegen E.W.,2007,Functional studies of Akt isoform specificity in skeletal muscle in vivo;maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression,Mol.Endocrinol.,21(1):215-228
Deng D.J.,2014,DNA methylation and demethylation:current status and future perspective,Yichuan(Hereditas),36(5):403-410(邓大君,2014,DNA甲基化和去甲基化的研究现状及思考,遗传),36(5):403-410)
Egerman M.A.,and Glass D.J.,2014,Signaling pathways controlling skeletal muscle mass,Crit.Rev.Biochem.Mol.Biol.,49(1):59-68
Hou W.Y.,Zhang Y.S.,Niu H.F.,and Xin Y.P.,2013,Epigenetic regulation of Akt gene on muscle cell development,Jiachu Shengtai Xuebao(Acta Ecologiae Animalis Domastici),34(4):6-9(侯伟媛,张云生,牛华锋,辛亚平,2013,Akt基因对肌肉细胞发育的表观调控,家畜生态学报,34(4):6-9)
Huang Y.Z.,Li M.X.,Wang J.,Zhan Z.Y.,Sun Y.J.,Sun J.J.,Li C.J.,Lan X.Y.,Lei C.Z.,Zhang C.L.,and Chen H.,2013,A5'-regulatory region and two coding region polymorphisms modulate promoter activity and gene expression of the growth suppressor gene ZBED6 in cattle,PLoS One,8(11):e79744
Huang Y.Z.,Sun J.J.,Zhang L.Z.,Li C.J.,Womack J.E.,Li Z.J.,Lan X.Y.,Lei C.Z.,Zhang C.L.,Zhao X.,and Chen H.,2014,Genome-wide DNA methylation profiles and their relationships with m RNA and the microRNA transcriptome in bovine muscle tissue(Bos taurine),Scientific Reports,4:6546
Ji M.,Zhang Q.,Ye J.W.,Wang X.Y.,Yang W.,and Zhu D.H.,2008,Myostatin induces p300 degradation to silence cyclin D1 expression through the PI3K/PTEN/Akt pathway,Cell Signal,20(8):1452-1458
Li Jing,Zhang Y.S.,Li N.,Hu X.X.,Shi G.Q.,Liu S.R.,and Liu N.,2013,Expression of Myogenin and MCK genes regulated by PI3K/AKT pathway,Yichuan(Hereditas),35(5):637-642(李晶,张云生,李宁,胡晓湘,石国庆,刘守仁,柳楠,2013,PI3K/AKT信号通路调控Myogenin和MCK基因的表达,遗传,35(5):637-642)
Li Z.B.,Kollias H.D.,and Wagner K.R.,2008,Myostatin directly regulates skeletal muscle fibrosis,J.Biol.Chem.,283(28):19371-19378
Obrochta K.M.,Krois C.R.,Campos B.,and Napoli J.L.,2015,Insulin regulates retinol dehydrogenase expression and alltrans-retinoic acid biosynthesis through Fox O1,J.Biol.Chem.,290(11):7259-7268
Orlando D.A.,Chen M.W.,Brown V.E.,Solanki S.,Choi Y.J.,Olson E.R.,Fritz C.C.,Bradner J.E.,and Guenther M.G.,2014,Quantitative ChIP-Seq normalization reveals global modulation of the epigenome,Cell Rep.,9(3):1163-1170
Pansters N.A.,Schols A.M.,Verhees K.J.,de Theije C.C.,Snepvangers F.J.,Kelders M.C.,Ubags N.D.,Haegens A.,and Langen R.C.,2015,Muscle-specific GSK-3βablation accelerates regeneration of disuse-atrophied skeletal muscle,Biochim.Biophys.Acta,Mar.,1852(3):490-506
Serra C.,Palacios D.,Mozzetta C.,Forcales S.V.,Morantte I.,Ripani M.,Jones D.R.,Du K.Y.,Jhala U.S.,Simone C.,and Puri P.L.,2007,Functional interdependence at the chromatin level between the MKK6/p38 and IGF1/PI3K/AKT pathways during muscle differentiation,Mol.Cell,28(2):200-213
Shi J.,Luo L.Q.,Eash J.,Ibebunjo C.,and Glass D.J.,2011,The SCF-Fbxo40 complex induces IRS1 ubiquitination in skeletal muscle,limiting IGF1 signaling,Dev.Cell,21(5):835-847
Song B.Y.,and Zhu W.G.,2011,Advances in effector protein of histone methylation,Yichuan(Hereditas),33(4):285-292(宋博研,朱卫国,2011,组蛋白甲基化修饰效应分子的研究进展,遗传,33(4):285-292)
Wang R.X.,and Xu J.H.,2014,Genomic DNA methylation and histone methylation,Yichuan(Hereditas),36(3):191-199(王瑞娴,徐建红,2014,基因组DNA甲基化及组蛋白甲基化,遗传,36(3):191-199)
Ye Y.,Jin L.,Wilmott J.S.,Hu W.L.,Yosufi B.,Thorne R.F.,Liu T.,Rizos H.,Yan X.G.,Dong L.,Tay K.H.,Tseng H.Y.,Guo S.T.,de Bock C.E.,Jiang C.C.,Wang C.Y.,Wu M.,Zhang L.J.,Hersey P.,Scolyer R.A.,and Zhang X.D.,2013,PⅠ(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma,Nat.Commun.,4:1508
Zeng T.,Zhang C.L.,Song F.Y.,Zhao X.L.,and Xie K.Q.,2014,CM Z reversed chronic ethanol-induced disturbance of PPAR-αpossibly by suppressing oxidative stress and PGC-1αacetylation,and activating the MAPK and GSK3βpathway,PLoSOne,9(6):e98658