PTEN在脑胶质瘤中的研究进展

本文叙述了当前国内外抑癌基因 PTEN(phosphatase and tensin homology deleted on chromosome ten,PTEN)在胶质瘤细胞中的信号传导通路的最新进展.文中阐述了 PTEN 的分子结构、胶质瘤中的表达、相关信号传导通路以及在胶质瘤的发生、侵袭、增殖、凋亡等中的作用.研究表明,PTEN 对于胶质瘤的早期诊断和对胶质瘤的基因治疗可能具有重要的意义.     

抑癌基因PTEN在胃癌中的研究进展

近年来国内外的学者在多种肿瘤中发现抑癌基因PTEN的等位基因缺失、基因突变、甲基化,PTEN基因杂合性丢失(LOH)频繁的发生于胃癌,而该基因发生突变的频率较低,蛋白表达普遍下降.抑癌基因PTEN异常与胃癌的发生和发展相关,对PTEN功能的进一步研究将为胃癌的诊断和治疗提供新的思路.     

PTEN和mTOR信号转导通路在实验性脊髓损伤中的表达

目的:研究mTOR和PTEN蛋白在实验性脊髓损伤中的表达及其在脊髓损伤发生、发展中的作用.方法:用免疫组织化学方法和RT-PCR法,检测脊髓组织内mTOR和PTEN的表达.结果:与正常组织相比,免疫组化法和RT-PCR两种方法结果均显示,脊髓损伤后mTOR表达明显下降,而PTEN的表达明显增加;两者呈负相关(r=0.862,P＜0.01).结论:PI3 K/PTEN/AKT/mTOR信号转导通路中重要的调节位点和节点PTEN在实验性脊髓损伤中的表达明显增高,而mTOR的表达明显降低.提示该信号转导通路在介导实验性脊髓损伤的发生、发展的过程中起重要作用.     

蛋白组氨酸磷酸酶研究进展

主要概括磷酸酶的种类,原核细胞磷酸组氨酸生物功能及调控,哺乳动物组氨酸残基磷酸化、去磷酸化,以及组氨酸磷酸酶及其底物的最新研究进展. 信号转导在生长发育及细胞功能中起极其重要的作用. 无论在原核还是真核细胞,蛋白质磷酸化是细胞内信号转导的关键机制. 研究最多的可逆的真核蛋白磷酸化,主要发生在含有羟基的丝氨酸、苏氨酸和酪氨酸残基上. 不同的激酶和磷酸酶受不同机制的调节,而调节过程中出现的差异是人类很多疾病的潜在基础. 与大量有关羟基磷酸化氨基酸的报道相比,有关氨基磷酸化氨基酸的报道甚少. 据估计,自然界中存在的磷酸组氨酸比磷酸酪氨酸多10 ~ 100倍,但不如磷酸丝氨酸丰富. 虽然对脊椎动物蛋白质中存在磷酸组氨酸的认识可以追溯到20世纪60年代初, 但由于研究手段的限制,至今对脊椎动物蛋白组氨酸激酶及组氨酸磷酸酶的结构及功能知之甚少. 但是,近几年的研究有突破性的发现,克隆和重组表达哺乳动物组氨酸磷酸酶为研究氨基磷酸化氨基酸的生物功能翻开新的一章.     

胚胎干细胞磷酸酶的研究进展

胚胎干细胞磷酸酶(embryonic stem cell phosphatase,ESP)是在骨、性腺、胚胎等组织中高表达的一种跨膜受体样蛋白酪氨酸磷酸酶。研究表明ESP可能介导细胞分化以及细胞间相互作用的信号转导,参与成骨细胞以及生殖细胞的分化过程。ESP还能够抑止肿瘤细胞生长、抑制癌症发生。近年的研究发现ESP可通过在成骨细胞中的特异性表达影响骨钙素的活性从而调节胰岛素的分泌和敏感性,提示ESP在骨骼的内分泌功能中起重要作用,并参与骨骼对机体能量代谢稳态的调节。     

植物蛋白磷酸酶及其在植物抗逆中的作用

随着多种蛋白磷酸酶在植物中的发现,可逆磷酸化作用在植物各种生理活动中的研究有许多重要的进展。本文概述了蛋白磷酸酶的类型与特点,并着重介绍近年来植物中多种磷酸酶的活性、基因、蛋白等各个水平上的鉴定工作。讨论了几类主要蛋白磷酸酶参与植物抵抗逆境胁迫的有关研究成果。     

蛋白磷酸酶2A在真菌细胞中的研究进展

蛋白质可逆的磷酸化修饰在真菌细胞生命活动中发挥着重要作用.磷酸化与去磷酸化过程相互协调.蛋白质中磷酸丝氨酸/苏氨酸位点的去磷酸化反应主要由蛋白磷酸酶2A(Protein Phosphatase 2A,PP2A)负责催化.PP2A由催化亚基、调节亚基与结构亚基组合成有活性的三聚体全酶形式发挥功能.本文以模式真菌酿酒酵母、...     

植物蛋白磷酸酶及其在植物抗逆中的作用

随着多种蛋白磷酸酶在植物中的发现,可逆磷酸化作用在植物各种生理活动中的研究有许多重要的进展。本文概述了蛋白磷酸酶的类型与特点,并着重介绍近年来植物中多种磷酸酶的活性、基因、蛋白等各个水平上的鉴定工作。讨论了几类主要蛋白磷酸酶参与植物抵抗逆境胁迫的有关研究成果。     

神经系统中的肿瘤抑制因子PTEN

PTEN是定位于10q23的第一个具有磷酸酶活性的抑癌基因,它能通过PI3K/AKT、FAK和MAPK信号转导通路调节细胞的生长、凋亡、迁移和转化。PTEN在神经系统的神经元中有广泛表达,其在调节神经干细胞的增殖、SVZ前体细胞的迁移及凋亡、PC12细胞的分化和神经突触的建立方面具有重要作用。因此,对PTEN功能的进一步研究将为肿瘤和神经性疾病的治疗提供新的思路。     

Phosphoprotein phosphatase in the central nervous system of Manduca sexta.

The existence and some enzymological properties of phosphoprotein phosphatase (EC 3.1.3.16) have been established in the larval central nervous system of the tobacco hornworm, Manduca sexta (Lepidoptera: Sphingidae). A simple, sensitive and reproducible assay employing 32-P-labeled protamine as a phosphoprotein substrate was employed to measure phosphatase activity in both soluble and particulate fractions of the insect nerve cord. The specific activity of soluble phosphatase in the Manduca sexta central nervous system is of the same order of magnitude as that in mammalian brain. Nerve cord phosphoprotamine phosphatase activity may be stimulated by a variety of monovalent salts, the optimal concentration of NaCl or KCl being 0.2 molar. Activity does not appear to be dependent on bivalent metals and is stimulated by EDTA. A reduced sulfhydryl group is obligatory for maximum activity. Phosphatase could be greatly inhibited by sodium fluoride, ATP and GTP. Cyclic AMP and cyclic GMP are without effect on enzyme activity. Although most of the phosphatase activity in the insect nerve cord appears to be of cytosolic origin, much latent activity can be unmasked by incubating membranous fractions with Triton X-100. In contrast to soluble phosphatase, the detergent-solubilized activity is moderately stimulated by Mn-2+.?     

组织型激肽释放酶及相关肽酶在中枢神经系统中的作用

组织型激肽释放酶1(kallikrein1,KLK1)和激肽释放酶相关肽酶(kallikrein-related peptidase 2～15,KLK2～15)是一类丝氨酸蛋白酶,具有广泛的生物学活性。在中枢神经系统中,它们不但在脑的生长、发育和学习记忆等方面起重要作用,同时也在多种脑部疾病中起重要作用,如帕金森病、痴呆、多发性硬化、肿瘤等,并在这些疾病的诊断、治疗和预后方面显示出潜在的应用价值。     

Electron microscopical demonstration of acid phosphatase activity in the central nervous system

Summary A modified technique is described for the demonstration of acid phosphatase activity in the central nervous system by means of electron microscopy. Enzyme activity can be demonstrated in lysosomes, pigment bodies, and the Golgi zone of cortical neurons. Glial and endothelial cells also contain acid phosphatase active lysosomes. They are located in the pericarya, and in the processes of the glial cells, respectively.The authors express their sincere appreciation to FräuleinS. Luh and FräuleinW. Komp for their assistance and help.     

SOCS家族在中枢神经系统的研究进展

细胞因子信号抑制因子（SOCS）家族是一类对细胞因子信号通路具有负反馈调节作用的蛋白分子,参与多种细胞因子、生长因子和激素的信号调节。细胞因子对中枢神经系统中的各种生物效应具有广泛多样的调节作用,SOCS家族的许多成员在发育时期和成年的脑内均有表达,SOCS家族不仅与细胞因子信号调节及中枢神经系统多种功能的调节密切相关,而且可能是神经发育和分化的重要调控因子,并参与神经免疫内分泌调节。本文综述了SOCS家族的发现、结构特点、脑内分布以及在中枢神经系统中的功能等方面的研究进展。     

肠道菌群与中枢神经系统相互作用及相关疾病

肠道菌群参与宿主的多项生理过程,包括营养物质吸收、代谢及免疫系统的发育成熟、抵抗外来病原体入侵等,新的研究显示肠道菌群通过神经、内分泌、代谢和免疫的途径参与了肠道和中枢神经系统的双向调节。肠道菌群的变化与自闭症、多发性硬化、帕金森病、焦虑和抑郁症等一系列神经精神疾病有关,通过改善肠道菌群的微生态疗法有望成为治疗和预防一些神经系统疾病的有效措施。     

Selected clinical research involving the central nervous system

This paper updates three clinical research projects involving the central nervous system. Discussions of conditions with encephalocele include several associations: encephalocele/craniostenosis, transsphenoidal encephalocele/hypothalamic-pituitary dysfunction, encephalocele/oculo-auriculo-vertebral spectrum, and encephalocele/frontonasal dysplasia. The relationship between oculo-auriculo-vetebral spectrum with encephalocele and frontonasal dysplasia with epibulbar dermoids and ear tags is also discussed and an explanation for encephalocele formation in the Apert syndrome is provided. Studies of the central nervous system in Apert syndrome indicate that distortion ventriculomegaly is common, but progressive hydrocephalus occurs infrequently. A recurrent pattern of abnormalities was discerned consisting of megalencephaly, gyral abnormalities, and defects of the corpus callosum and limbic structures. Five neuropathologic studies lend further support to this pattern of CNS anomalies in the Apert syndrome. In a study of holoprosencephaly, eight principles governing associated facial dysmorphism were derived. Each diagnostic category was shown to have its own frequency and range of holoprosencephalic faces. Some categories, such as del(13q), have narrow ranges; others, such as trisomy 13 syndrome, have broad ranges. However, no broad diagnostic range is known to include agnathia-holoprosencephaly and other severe forms of facial dysmorphism without agnathia. Absent maxillary incisors and a single maxillary central incisor are extremely common in holoprosencephaly with severe facial dysmorphism and may occur on occasion as a striking microform of holoprosencephaly, most commonly in the autosomal dominant form.     

The lipid phosphatase activity of PTEN is critical for stabilizing intercellular junctions and reverting invasiveness.

To analyze the implication of PTEN in the control of tumor cell invasiveness, the canine kidney epithelial cell lines MDCKras-f and MDCKts-src, expressing activated Ras and a temperature-sensitive v-Src tyrosine kinase, respectively, were transfected with PTEN expression vectors. Likewise, the human PTEN-defective glioblastoma cell lines U87MG and U373MG, the melanoma cell line FM-45, and the prostate carcinoma cell line PC-3 were transfected. We demonstrate that ectopic expression of wild-type PTEN in MDCKts-src cells, but not expression of PTEN mutants deficient in either the lipid or both the lipid and protein phosphatase activities, reverted the morphological transformation, induced cell-cell aggregation, and suppressed the invasive phenotype in an E-cadherin-dependent manner. In contrast, overexpression of wild-type PTEN did not counteract Ras-induced invasiveness of MDCKras-f cells expressing low levels of E-cadherin. PTEN effects were not associated with marked changes in accumulation or phosphorylation levels of E-cadherin and associated catenins. Wild-type, but not mutant, PTEN also reverted the invasive phenotype of U87MG, U373MG, PC-3, and FM-45 cells. Interestingly, PTEN effects were mimicked by N-cadherin-neutralizing antibody in the glioblastoma cell lines. Our data confirm the differential activities of E- and N-cadherin on invasiveness and suggest that the lipid phosphatase activity of PTEN exerts a critical role in stabilizing junctional complexes and restraining invasiveness.