细胞信号通路大全

细胞信号通路的基本组成受体介导细胞信号通路包括：a.CAMP信号通路：由CM上的五种组分组成——激活型激素受体，Rs；与GDP结合的活化型调蛋白，Gs；腺来自苷酸环化酶，c；与G演他攻看很委酒继钢亮DP结合的抑制型调节蛋白，Gi；抑制型激素受体，Ri。

激素配体+Rs→Rs构象改变暴露出与Gs结合位点→与Gs结合→Gs2变化排斥GDP结合GTP360问答而活化→使三聚体Gs解离出α和βγ→暴露出α与腺苷酸环化酶结合位点→与A 环化E结合并使之活化→将ATP→CAMP→激活靶酶和开启基因表达→GTP水解，α恢复构象与A环化酶解离→C的环化作用终止→α和βγ结合回复。

pip2信号通路：胞外signal+膜受体→PIP2IP3+DAG，IP3→内源钙→细胞溶质，胞内Ca2+浓度升高→启动Ca2+信号系统，DAGCM上活化蛋白激酶PKC→DG/PKC信号传递passwa。

细胞信号转导特点是了望析学省却析班：①高度亲和力，②高度特异性，③可饱和性1、受体：位于细胞膜上或细胞内，能特异性识别生物活性分子并与之结合，进而引起生物学效应的特殊蛋白质，膜受体多为镶嵌糖蛋白：胞内受体全部为DNA结合蛋白。

受体在细胞信息传递过程中起极为重要的作用。

2、G蛋白：即鸟苷酸结合蛋白，是一类位于细胞膜胞浆面、能与GDP或GTP结合的外周蛋白，由α、β、γ三个亚基组成。

以三聚体存在并与GDP结合者为非活化型。

当α亚基与GTP结合并导致βγ二聚体脱落时则变成活化型，可作用于面膜受体的不同激素,通过不同的G蛋白介导影响农场慢开你质膜上某些离子通道或酶的活性，继而影响细胞内第二信使浓度和后续的生物学效应。

第一个和第二个都是G蛋白偶连信号通路,第三个是与酶偶连的信号通路1、cAMP信号通路信号分子与受体结合后，通过与GTP结合的调节蛋白(G蛋白)的耦联，在细胞内产生第二信使，从而引起细胞的应答反应。

cAMP信号通路由质膜上的5种成分组成：①激活型激素受体(Rs)；②抑制型激素受体(Ri)；③与GDP结合的活化型调节蛋白(Gs)；④与GDP 的抑制型调节蛋白(Gi)；⑤腺苷酸环化酶( C )。

细胞信号转导通路梳理在我们的身体中，细胞就像是一个个小社会，它们之间不断地进行着信息交流和传递，以协调各种生理活动和应对外界环境的变化。

这种细胞之间的信息传递过程，被称为细胞信号转导。

细胞信号转导通路就像是一条条复杂的“信息高速公路”，将各种信号从细胞外传递到细胞内，引发一系列的反应，从而影响细胞的命运和功能。

细胞信号转导通路可以大致分为三类：离子通道型受体介导的信号转导通路、G 蛋白偶联受体介导的信号转导通路和酶联型受体介导的信号转导通路。

离子通道型受体介导的信号转导通路相对较为直接。

这类受体本身就是离子通道，当配体与受体结合后，通道的构象发生改变，导致离子的跨膜流动，从而快速地将信号传递到细胞内。

比如，神经细胞中的乙酰胆碱受体就是一种离子通道型受体。

当乙酰胆碱与受体结合时，钠离子迅速内流，引发神经冲动的传递。

G 蛋白偶联受体介导的信号转导通路则要复杂一些。

G 蛋白偶联受体位于细胞膜上，当配体与受体结合后，受体发生构象变化，从而激活与之偶联的 G 蛋白。

G 蛋白是由α、β、γ三个亚基组成的三聚体，根据α亚基的不同，可以分为 Gs、Gi、Gq 等多种类型。

激活后的 G蛋白可以进一步激活或抑制下游的效应酶，如腺苷酸环化酶、磷脂酶C 等，从而产生第二信使，如 cAMP、IP3、DAG 等。

这些第二信使再进一步激活蛋白激酶等信号分子，最终将信号传递到细胞内的各个部位，调节细胞的生理功能。

以 cAMP 信号通路为例，当配体与 G 蛋白偶联受体结合后，激活Gs 蛋白，Gs 蛋白激活腺苷酸环化酶，使细胞内的ATP 转化为cAMP。

cAMP 作为第二信使，可以激活蛋白激酶 A（PKA），PKA 可以磷酸化多种靶蛋白，从而调节细胞的代谢、基因表达等生理过程。

酶联型受体介导的信号转导通路则更加多样化。

这类受体的胞内段具有酶的活性，或者与酶相偶联。

常见的酶联型受体包括受体酪氨酸激酶（RTK）、受体丝氨酸/苏氨酸激酶、受体酪氨酸磷酸酯酶、受体鸟苷酸环化酶等。

1 PPAR信号通路：过氧化物酶体增殖物激活受体( PPARs) 是与维甲酸、类固醇和甲状腺激素受体相关的配体激活转录因子超家族核激素受体成员。

它们作为脂肪传感器调节脂肪代谢酶的转录。

PPARs由PPARα、PPARβ和PPARγ 3种亚型组成。

PPARα主要在脂肪酸代谢水平高的组织，如：肝、棕色脂肪、心、肾和骨骼肌表达。

他通过调控靶基因的表达而调节机体许多生理功能包括能量代谢、生长发育等。

另外，他还通过调节脂质代谢的生物感受器而调节细胞生长、分化与凋亡。

PPARa同时也是一种磷酸化蛋白，他受多种磷酸化酶的调节包括丝裂原激活蛋白激酶( ERK-和p38．M APK) ，蛋白激酶A和C( PKA，PKC) ，AM PK和糖原合成酶一3( G SK3) 等调控。

调控PPARa生长信号的酶报道有M APK、PKA和G SK3。

PPARβ广泛表达于各种组织，而PPAR γ主要局限表达在血和棕色脂肪，其他组织如骨骼肌和心肌有少量表达。

PPAR-γ在诸如炎症、动脉粥样硬化、胰岛素抵抗和糖代谢调节，以及肿瘤和肥胖等方面均有着举足轻重的作用，而其众多生物学效应则是通过启动或参与的复杂信号通路予以实现。

鉴于目前人们对PPAR—γ信号通路尚不甚清，PPARs 通常是通过与9-cis维甲酸受体( RXR)结合实现其转录活性的。

2 MAPK信号通路:mapk简介:丝裂原激活蛋白激酶（mitogen—activated protein kinase，MAPK）是广泛存在于动植物细胞中的一类丝氨酸/苏氨酸蛋白激酶。

作用主要是将细胞外刺激信号转导至细胞及其核内，并引起细胞的生物化学反应（增殖、分化、凋亡、应激等）。

MAPKs家族的亚族 :ERKs（extracellular signal regulated kinase)：包括ERK1、ERK2。

生长因子、细胞因子或激素激活此通路，介导细胞增殖、分化。

JNKs(c-Jun N-terminal kinase)包括JNK1、JNK2、JNK3。

细胞信号转导通路的分子机制和调节细胞信号转导通路是生命科学中一个重要的研究领域。

它是指通过特定的信号分子和受体，从外部环境接收信息，经由一系列分子信号传递，最终影响细胞的基因表达和功能，进而影响细胞的生理和病理状态。

研究细胞信号转导通路的分子机制和调节，对于理解细胞的生物学功能、疾病的发生和治疗具有重要的意义。

一、细胞信号转导通路的分子机制细胞信号转导通路包括多种分子机制，如激酶、酵素、信号蛋白、离子通道等，这些分子机制可以形成多种信号通路。

1. 激酶通路激酶通路是细胞中一个常见的信号传导方式。

激酶通路包括多种激酶，如胰岛素受体激酶、丝裂原活化激酶（MAPK）等。

当激酶受到激活的信号分子作用后，它们会磷酸化一个细胞内信号蛋白或转录因子，并影响它们的功能和位置，进而影响细胞代谢和基因表达。

激酶通路在许多生物学过程中都扮演着重要的角色，比如细胞增殖、分化、凋亡等。

2. 核受体通路核受体通路是一种通过特定的核受体介导的信号转导方式。

这些核受体包括雄激素受体、雌激素受体、甲状腺素受体等等。

当这些核受体受到特定的激活信号分子作用后，它们发生构象变化，从而导致与其结合的蛋白与DNA相互作用，进而影响细胞的转录和转录后加工过程。

3. 离子通道通路离子通道通路是一种通过特定类型的离子通道介导的信号传导机制。

离子通道是细胞膜上的特定通道蛋白，可以通过通道内的离子流动改变细胞内外液体的离子化学平衡以及细胞膜电位，从而影响细胞的生物学功能。

二、细胞信号转导通路的调节细胞信号转导通路的调节是指一些信号分子对信号通路进行控制和修饰，调节通路过程或作用，从而影响细胞生物学功能和特异性。

信号通路的调节有多种形式。

1. 磷酸化修饰磷酸化修饰是细胞信号转导中最常见的分子调节方式之一。

磷酸化一般是通过激酶将磷酸基团附加到目标蛋白的羟基残基上，或通过去磷酸化酶从目标蛋白上去除已有的磷酸基团。

磷酸化修饰能够影响目标蛋白的结构和功能，从而影响信号通路的传递和响应。

细胞信号转导通路的不同类型细胞信号转导通路是细胞内的一种复杂的动态过程，它通过传递化学信息，引导细胞作出生理反应。

在细胞内，各种各样的信号通路网络呈现出不同的形态和类型，这些通路的启动和终止都受到多种因素的影响。

下面我们将着重讨论细胞信号转导通路的不同类型。

简单的传递通路简单的传递通路是指信号通路中只有一个中间环节或目标信号分子，例如胰岛素信号。

当胰岛素结合到细胞膜上的胰岛素受体上时，受体活化，使得内部酶被活化，进而催化葡萄糖从血液中转运到细胞内进行利用。

这个通路的转导是相对较简单的，只涉及单个目标分子。

级联式通路级联式通路是最常见的信号转导通路。

它包含多个步骤，每个步骤都需要激活前一步骤的分子以及目标分子。

它的其中一个典型例子就是MAPK通路。

这个通路引导细胞响应各种刺激，如压力、炎症、缺氧等。

当外在信号被检测到时，受体会被激活，将信号传递到一系列下游蛋白中，最后激活细胞核中的转录因子，以产生相应的基因表达。

环形信号转导通路环形信号转导通路是指信号从蛋白质开始，沿着一系列的酶、途径、交换因子再到达相同的蛋白质。

这种环路通路的最公认例子就是G蛋白耦合受体通路。

当足够的荷尔蒙或药物结合到G蛋白偶联受体时，受体激活经过甲状腺素、钙、cAMP (环磷酸腺苷)、PKA等一系列交换因子转化，最终以相同的受体进行转导，反复产生本体差异效应。

核受体信号转导通路核受体信号转导通路是由细胞内的溶质或激素所引发的反应，在这种反应中，受体被激活，进入细胞内，与核受体结合。

这种反应可以引起目标基因的转录，例如睾酮的作用。

睾酮被检测到后，通过激活核受体引发的反应使得蛋白质复合物形成，总体上增加了基因表达水平。

总之，细胞信号传导通路总体上由多种因素的集合影响。

每个信号转导通路都是由一系列复杂的调节机制所组成的。

对不同类型信号转导通路的深入理解有助于设计更好的药物，并广泛应用于医学、农业等领域。

细胞信号通路的理论和应用细胞信号通路指的是细胞内外物质之间的信息传递机制。

这些信息可以通过化学物质或者物理信号的形式传递。

这种信号传递过程对于细胞的生理和病理过程起着至关重要的作用。

细胞信号通路的研究是现代生物学重要的研究方向之一。

本文将分别从理论和应用两个方面进行介绍。

一、细胞信号通路的理论1.信号传导的类型细胞信号可以通过细胞内和细胞外的化学物质进行传递。

细胞内信号通路包括直接的细胞膜通道，酶反应，离子通道等；而细胞外信号通路包括激素，神经递质以及生物活性物质等。

这些信号可以通过各种信号途径进行传递，最终作用于细胞内的信号传导途径，进而影响细胞的代谢和功能。

2.信号转导的机制信号转导是信息从细胞膜到细胞核的传递过程。

这个过程中，信号分子在物理上与受体分子进行绑定。

此后，分子会激活一个酶反应阶段，从而引导信号从受体到活化酶的传递。

当信号到达细胞核时，它将影响基因表达和细胞生理过程。

3.信号通路的分类细胞信号通路可以分为两大类：内源性通路和外源性通路。

内源性通路是指细胞内部因子对细胞的影响，包括细胞周期的调控，细胞凋亡和细胞形态的调节等。

而外源性通路则是指从周围环境中引入的化学因子和物理因子，如细胞因子，激素，氧气，光线等。

这些环境因素通过作用于细胞表面的受体激活信号通路，进而影响细胞内的生理过程。

二、细胞信号通路的应用1.肿瘤治疗中的应用细胞信号通路在肿瘤治疗过程中的应用已经得到了长期的研究。

白血病、卵巢癌和肺癌等疾病的治疗中，靶向信号通路的药物已经得到了广泛的应用。

靶向细胞信号通路可以通过抑制细胞生长和凋亡来帮助控制癌细胞的发展。

这种药物可以通过选择性作用于癌细胞的外在和内在的生长和发展因素，从而帮助通过靶向信号通路来攻击癌症细胞。

2.神经退行性疾病的治疗信号通路在神经退行性疾病治疗中也得到了广泛的应用。

在老年痴呆症等疾病的治疗中，对神经信号通路进行靶向治疗可以帮助改善病人的神经系统活动和参数。

目录actin肌丝...........................................................Wnt/LRP6?信号.......................................................WNT信号转导.........................................................West?Nile?西尼罗河病毒..............................................Vitamin?C?维生素C在大脑中的作用....................................视觉信号转导........................................................VEGF，低氧..........................................................TSP-1诱导细胞凋亡...................................................Trka信号转导........................................................dbpb调节mRNA .......................................................CARM1甲基化.........................................................CREB转录因子........................................................TPO信号通路.........................................................Toll-Like?受体......................................................TNFR2?信号通路......................................................TNFR1信号通路.......................................................IGF-1受体...........................................................TNF/Stress相关信号..................................................共刺激信号..........................................................Th1/Th2?细胞分化....................................................TGF?beta?信号转导...................................................端粒、端粒酶与衰老..................................................TACI和BCMA调节B细胞免疫...........................................T辅助细胞的表面受体.................................................T细胞受体信号通路...................................................T细胞受体和CD3复合物............................................... Cardiolipin的合成...................................................Synaptic突触连接中的蛋白............................................HSP在应激中的调节的作用.............................................Stat3?信号通路......................................................SREBP控制脂质合成...................................................酪氨酸激酶的调节....................................................Sonic?Hedgehog?(SHH)受体ptc1调节细胞周期...........................Sonic?Hedgehog?(Shh)?信号...........................................SODD/TNFR1信号......................................................AKT/mTOR在骨骼肌肥大中的作用........................................G蛋白信号转导.......................................................IL1受体信号转导.....................................................acetyl从线粒体到胞浆过程............................................趋化因子chemokine在T细胞极化中的选择性表达........................SARS冠状病毒蛋白酶..................................................SARS冠状病毒蛋白酶..................................................Parkin在泛素-蛋白酶体中的作用....................................... nicotinic?acetylcholine受体在凋亡中的作用........................... 线粒体在细胞凋亡中的作用............................................ MEF2D在T细胞凋亡中的作用........................................... Erk5和神经元生存.................................................... ERBB2信号转导....................................................... GPCRs调节EGF受体................................................... BRCA1调节肿瘤敏感性................................................. Rho细胞运动的信号................................................... Leptin能逆转胰岛素抵抗.............................................. 转录因子DREAM调节疼敏感............................................ PML调节转录......................................................... p27调节细胞周期..................................................... MAPK信号调节........................................................ 细胞因子调节造血细胞分化............................................ eIF4e和p70?S6激酶调节.............................................. eIF2调节............................................................ 谷氨酸受体调节ck1/cdk5 .............................................. BAD磷酸化调节....................................................... plk3在细胞周期中的作用.............................................. Reelin信号通路...................................................... RB肿瘤抑制和DNA破坏................................................ NK细胞介导的细胞毒作用.............................................. Ras信号通路......................................................... Rac?1细胞运动信号................................................... PTEN依赖的细胞生长抑制和细胞凋亡.................................... 蛋白激酶A（PKA）在中心粒中的作用.................................... notch信号通路....................................................... 蛋白酶体Proteasome复合物........................................... Prion朊病毒的信号通路............................................... 早老素Presenilin在notch和wnt信号中的作用......................... 淀粉样蛋白前体信号.................................................. mRNA的poly(A)形成.................................................. PKC抑制myosin磷酸化................................................ 磷脂酶C（PLC）信号.................................................. 巨噬细胞Pertussis?toxin不敏感的CCR5信号通路....................... Pelp1调节雌激素受体的活性........................................... PDGF信号通路........................................................ p53信号通路......................................................... p38MAPK信号通路..................................................... Nrf2是氧化应激基本表达的关键基因.................................... OX40信号通路........................................................ hTert转录因子的调节作用............................................. hTerc转录调节活性图................................................. AIF在细胞凋亡中的作用............................................... Omega氧化通路.......................................................核受体在脂质代谢和毒性中的作用...................................... NK细胞中NO2依赖的IL-12信号通路.................................... TOR信号通路......................................................... NO信号通路.......................................................... NF-kB信号转导通路................................................... NFAT与心肌肥厚的示意图.............................................. 神经营养素及其表面分子.............................................. 神经肽VIP和PACAP防止活化T细胞凋亡图.............................. 神经生长因子信号图.................................................. 细胞凋亡信号通路.................................................... MAPK级联通路........................................................ MAPK信号通路图...................................................... BCR信号通路......................................................... 蛋白质乙酰化示意图.................................................. wnt信号通路......................................................... 胰岛素受体信号通路.................................................. 细胞周期在G2/M期的调控机理图....................................... 细胞周期G1/S检查点调控机理图....................................... Jak-STAT关系总表.................................................... Jak/STAT?信号....................................................... TGFbeta信号......................................................... NFkappaB信号........................................................ p38?MAPK信号通路.................................................... SAPK/JNK?信号级联通路............................................... 从G蛋白偶联受体到MAPK .............................................. MAPK pathwayMAPK级联信号图.......................................... eIF-4E和p70?S6激酶调控蛋白质翻译................................... eif2蛋白质翻译...................................................... 蛋白质翻译示意图.................................................... 线粒体凋亡通路...................................................... 死亡受体信号通路.................................................... 凋亡抑制通路........................................................ 细胞凋亡综合示意图.................................................. Akt/Pkb信号通路..................................................... MAPK/ERK信号通路.................................................... 哺乳动物MAPK信号通路............................................... Pitx2多步调节基因转录............................................... IGF-1R导致BAD磷酸化的多个凋亡路径.................................. 多重耐药因子........................................................ mTOR信号通路........................................................ Msp/Ron受体信号通路................................................. 单核细胞和其表面分子................................................ 线粒体的肉毒碱转移酶（CPT）系统..................................... METS影响巨噬细胞的分化.............................................. Anandamide，内源性大麻醇的代谢...................................... 黑色素细胞（Melanocyte）发育和信号..................................DNA甲基化导致转录抑制的机理图....................................... 蛋白质的核输入信号图................................................ PPARa调节过氧化物酶体的增殖......................................... 对乙氨基酚（Acetaminophen）的活性和毒性机理......................... mCalpain在细胞运动中的作用.......................................... MAPK信号图.......................................................... MAPK抑制SMRT活化................................................... 苹果酸和天门冬酸间的转化............................................ 低密度脂蛋白（LDL）在动脉粥样硬化中的作用........................... LIS1基因在神经细胞的发育和迁移中的作用图............................ Pyk2与Mapk相连的信号通路........................................... galactose代谢通路................................................... Lectin诱导补体的通路................................................ Lck和Fyn在TCR活化中的作用......................................... 乳酸合成图.......................................................... Keratinocyte分化图.................................................. 离子通道在心血管内皮细胞中的作用.................................... 离子通道和佛波脂（Phorbal?Esters）信号.............................. 内源性Prothrombin激活通路.......................................... Ribosome内化通路.................................................... 整合素（Integrin）信号通路.......................................... 胰岛素（Insulin）信号通路........................................... Matrix?Metalloproteinases ........................................... 组氨酸去乙酰化抑制剂抑制Huntington病............................... Gleevec诱导细胞增殖................................................. Ras和Rho在细胞周期的G1/S转换中的作用.............................. DR3，4，5受体诱导细胞凋亡........................................... AKT调控Gsk3图...................................................... IL-7信号转导........................................................ IL22可溶性受体信号转导图............................................ IL-2活化T细胞图.................................................... IL12和Stat4依赖的TH1细胞发育信号通路.............................. IL-10信号通路....................................................... IL?6信号通路........................................................ IL?5信号通路........................................................actin肌丝Mammalian cell motility requires actin polymerization in the direction of movement to change membrane shape and extend cytoplasm into lamellipodia. The polymerization of actin to drive cell movement also involves branching of actin filaments into a network oriented with the growing ends of the fibers near the cell membrane. Manipulation of this process helps bacteria like Salmonella gain entry into cells they infect. Two of the proteins involved in the formation of Y branches and in cell motility are Arp2 and Arp3, both members of a large multiprotein complex containing several other polypeptides as well. The Arp2/3 complex is localized at the Y branch junction and induces actin polymerization. Activity of this complex is regulated by multiple different cell surface receptor signaling systems, activating WASP, and Arp2/3 in turn to cause changes in cell shape and cell motility. Wasp and its cousin Wave-1 interact with the Arp2/3 complex through the p21 component of the complex. The crystal structure of the Arp2/3 complex has revealed further insights into the nature of how the complex works.Activation by Wave-1, another member of the WASP family, also induces actin alterations in response to Rac1 signals upstream. Wave-1 is held in an inactive complex in the cytosol that is activated to allow Wave-1 to associate with Arp2/3. While WASP is activated by interaction with Cdc42, Wave-1, is activated by interaction with Rac1 and Nck. Wave-1 activation by Rac1 and Nck releases Wave-1 with Hspc300 to activate actin Y branching and polymerization by Arp2/3. Different members of this gene family may produce different actin cytoskeletal architectures. The immunological defects associated with mutation of the WASP gene, the Wiskott-Aldrich syndrome for which WASP was named, indicates the importance of this system for normal cellular function.Cory GO, Ridley AJ. Cell motility: braking WAVEs. Nature. 2002 Aug 15;418(6899):732-3. No abstract available.Eden, S., et al. (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418(6899), 790-3Falet H, Hoffmeister KM, Neujahr R, Hartwig JH. Normal Arp2/3 complex activation in platelets lacking WASp. Blood. 2002 Sep 15;100(6):2113-22.Kreishman-Deitrick M, Rosen MK, Kreishman-Deltrick M. Ignition of a cellular machine. Nat Cell Biol. 2002 Feb;4(2):E31-3. No abstract available.Machesky, L.M., Insall, R.H. (1998) Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol 8(25), 1347-56 Robinson, R.C. et al. (2001) Crystal structure of Arp2/3 complex. Science 294(5547), 1679-84Weeds A, Yeoh S. Structure. Action at the Y-branch. Science. 2001 Nov 23;294(5547):1660-1. No abstract available.Wnt/LRP6?信号Wnt glycoproteins play a role in diverse processes during embryonic patterning in metazoa through interaction with frizzled-type seven-transmembrane-domain receptors (Frz) to stabilize b-catenin. LDL-receptor-related protein 6 (LRP6), a Wnt co-receptor, is required for this interaction. Dikkopf (dkk) proteins are both positive and negative modulators of this signalingWNT信号转导West?Nile?西尼罗河病毒West Nile virus (WNV) is a member of the Flaviviridae, a plus-stranded virus family that includes St. Louis encephalitis virus, Kunjin virus, yellow fever virus, Dengue virus, and Japanese encephalitis virus. WNV was initially isolated in 1937 in the West Nile region of Uganda and has become prevalent in Africa, Asia, and Europe. WNV has rapidly spread across the United States through its insect host and causes neurological symptoms and encephalitis, which can result in paralysis or death. Since 1999 about 3700 cases of West Nile virus (WNV) infection and 200 deaths have been recorded in United States. The viral capsid protein likely contributes to theWNV-associated deadly inflammation via apoptosis induced through the mitochondrial pathway.WNV particles (50 nm in diameter) consist of a dense core (viral protein C encapsidated virus RNA genome) surrounded by a membrane envelope (viral E and M proteins embedded in a lipid bilayer). The virus binds to a specific cell surface protein (not yet identified), an interaction thought to involve E protein with highly sulfated neperan sulfate (HSHS) residues that are present on the surfaces of many cells and enters the cell by a process similar to that of endocytosis. Onceinside the cell, the genome RNA is released into the cytoplasm via endosomal release, a fusion process involving acidic pH induced conformation change in the E protein. The RNA genome serves as mRNA and is translated by ribosomes into ten mature viral proteins are produced via proteolytic cleavage, which include three structural components and seven different nonstructural components of the virus. These proteins assemble and transcribe complimentary minus strand RNAs from the genomic RNA. The complimentary minus strand RNA in turns serves as template for the synthesis of positive-stranded genomic RNAs. Once viral E, preM and C proteins have accumulated to sufficient level, they assemble with the genomic RNA to form progeny virions, which migrate to the cell surface where they are surrounded with lipid envelop and released.Vitamin?C?维生素C在大脑中的作用Vitamin C (ascorbic acid) was first identified by virtue of the essential role it plays in collagen modification, preventing the nutritional deficiency scurvy. Vitamin C acts as a cofactor for hydroxylase enzymes that post-translationally modify collagen to increase the strength and elasticity of tissues. Vitamin C reduces the metal ion prosthetic groups of many enzymes, maintaining activity of enzymes, also acts as an anti-oxidant. Although the prevention of scurvy through modification of collagen may be the most obvious role for vitamin C, it is not necessarily the only role of vitamin C. Svct1 and Svct2 are ascorbate transporters for vitamin C import into tissues and into cells. Both of these transporters specifically transport reduced L-ascorbic acid against a concentration gradient using the intracellular sodium gradient to drive ascorbate transport. Svct1 is expressed in epithelial cells in the intestine, upregulated in cellular models for intestinal epithelium and appears to be responsible for the import of dietary vitamin C from the intestinal lumen. The vitamin C imported from the intestine is present in plasma at approximately 50 uM, almost exclusively in the reduced form, and is transported to tissues to play a variety of roles.Svct2 imports reduced ascorbate from the plasma into very active tissues like the brain. Deletion in mice of the gene for Svct2 revealed that ascorbate is required for normal development of the lungs and brain during pregnancy. A high concentration of vitamin C in neurons of the developing brain may help protect the developing brain from free radical damage. The oxidized form of ascorbate, dehydroascorbic acid, is transported into a variety of cells by the glucose transporter Glut-1.Glut-1, Glut-3 and Glut-4 can transport dehydroascorbate, but may not transport significant quantities of ascorbic acid in vivo.视觉信号转导The signal transduction cascade responsible for sensing light in vertebrates is one of the best studied signal transduction processes, and is initiated by rhodopsin in rod cells, a member of the G-protein coupled receptor gene family. Rhodopsin remains the only GPCR whose structure has been resolved at high resolution. Rhodopsin in the discs of rod cells contains a bound 11-cis retinal chromophore, a small molecule derived from Vitamin A that acts as the light sensitive portion of the receptor molecule, absorbing light to initiate the signal transduction cascade. When light strikes 11-cis retinal and is absorbed, it isomerizes to all-trans retinal, changing the shape of the molecule and the receptor it is bound to. This change inrhodopsin抯 shape alters its interaction with transducin, the member of theG-protein gene family that is specific in its role in visual signal transduction. Activation of transducin causes its alpha subunit to dissociate from the trimer and exchange bound GDP for GTP, activating in turn a membrane-bound cyclic-GMP specific phosphodiesterase that hydrolyzes cGMP. In the resting rod cell, high levels of cGMP associate with a cyclic-GMP gated sodium channel in the plasma membrane, keeping the channels open and the membrane of the resting rod cells depolarized. This is distinct from synaptic generation of action potentials, in which stimulation induces opening of sodium channels and depolarization. When cGMP gated channels in rod cells open, both sodium and calcium ions enter the cell, hyperpolarizing the membrane and initiating the electrochemical impulse responsible for conveying the signal from the sensory neuron to the CNS. The rod cell in the resting state releases high levels of the inhibitory neurotransmitter glutamate, while the release of glutamate is repressed by the hyperpolarization in the presence of light to trigger a downstream action potential by ganglion cells that convey signals to the brain. The calcium which enters the cell also activates GCAP, which activates guanylate cyclase (GC-1 and GC-2) to rapidly produce more cGMP, ending the hyperpolarization and returning the cell to its resting depolarized state. A protein called recoverin helps mediate the inactivation of the signal transduction cascade, returning rhodopsin to its preactivated state, along with the rhodopsin kinase Grk1. Phosphorylation of rhodopsin by Grkl causes arrestin to bind, helping to terminate the receptor activation signal. Dissociation and reassociation of retinal, dephosphorylation of rhodopsin and release of arrestin all return rhodopsin to its ready state, prepared once again to respond to light.VEGF，低氧Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis such as tumor growth and ischemic diseases. Hypoxia is a potent inducer of VEGF in vitro. The increase in secreted biologically active VEGF protein from cells exposed to hypoxia is partly because of an increased transcription rate, mediated by binding of hypoxia-inducible factor-1 (HIF1) to a hypoxia responsive element in the 5'-flanking region of theVEGF gene. bHLH-PAS transcription factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1a) product. HLF mRNA expression is closely correlated with that of VEGF mRNA.. The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung. VEGF expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mRNA. HuR binds with high affinity and specificity to the VRS element that regulates VEGF mRNA stability by hypoxia. In addition, an internal ribosome entry site (IRES) ensures efficient translation of VEGF mRNA even under hypoxia. The VHL tumor suppressor (von Hippel-Lindau) regulates also VEGF expression at apost-transcriptional level. The secreted VEGF is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies.TSP-1诱导细胞凋亡As tissues grow they require angiogenesis to occur if they are to be supplied with blood vessels and survive. Factors that inhibit angiogenesis might act as cancer therapeutics by blocking vessel formation in tumors and starving cancer cells. Thrombospondin-1 (TSP-1) is a protein that inhibits angiogenesis and slows tumor growth, apparently by inducing apoptosis of microvascular endothelial cells that line blood vessels. TSP-1 appears to produce this response by activating a signaling pathway that begins with its receptor CD36 at the cell surface of the microvascular endothelial cell. The non-receptor tyrosine kinase fyn is activated by TSP-1 through CD36, activating the apoptosis inducing proteases like caspase-3 and p38 protein kinases. p38 is a mitogen-activated kinase that also induces apoptosis in some conditions, perhaps through AP-1 activation and the activation of genes that lead to apoptosis.Trka信号转导Nerve growth factor (NGF) is a neurotrophic factor that stimulates neuronal survival and growth through TrkA, a member of the trk family of tyrosine kinase receptors that also includes TrkB and TrkC. Some NGF responses are also mediated or modified by p75LNTR, a low affinity neurotrophin receptor. Binding of NGF to TrkA stimulates neuronal survival, and also proliferation. Pathways coupled to these responses are linked to TrkA through association of signaling factors with specific amino acids in the TrkA cytoplasmic domain. Cell survival through inhibition of apoptosis is signaled through activation of PI3-kinase and AKT. Ras-mediated signaling and phospholipase C both activate the MAP kinase pathway to stimulate proliferation.dbpb调节mRNAEndothelial cells respond to treatment with the protease thrombin with increased secretion of the PDGF B-chain. This activation occurs at the transcriptional level and a thrombin response element was identified in the promoter of the PDGF B-chain gene. A transcription factor called the DNA-binding protein B (dbpB) mediates the activation of PDGF B-chain transcription in response to thrombin treatment. DbpB is a member of the Y box family of transcription factors and binds to both RNA and DNA. In the absence of thrombin, endothelial cells contain a 50 kD form of dbpB that binds RNA in the cytoplasm and may play a role as a chaperone for mRNA. The 50 kD version of dbpB also binds DNA to regulate genes containing Y box elements in their promoters. Thrombin activation results in the cleavage of dbpB to a 30 kD form. The proteolytic cleavage releases dbpB from RNA in the nucleus, allowing it to enter the nucleus and binds to a regulatory element distinct from the site recognized by the full length 50 kD dbpB. The genes activated by cleaved dbpB include the PDGF B chain. Dephosphorylation of dbpB also regulates nuclear entry and transcriptional activation.RNA digestion in vitro can release dbpB in its active form, suggesting that the protease responsible for dbpB may be closely associated in a complex. Identification of the protease that cleaves dbpB, the mechanisms of phosphorylation and dephosphorylation, and elucidation of the signaling path by which thrombin induces dbpB will provide greater understanding of this novel signaling pathway.CARM1甲基化Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms ofpost-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known.CREB转录因子The transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including neurotransmitters, hormones, membrane depolarization, and growth and neurotrophic factors. Protein kinase A and the calmodulin-dependent protein kinases CaMKII stimulate CREB phosphorylation at Ser133, a key regulatory site controlling transcriptional activity. Growth and neurotrophic factors also stimulate CREB phosphorylation at Ser133. Phosphorylation occurs at Ser133 via p44/42 MAP Kinase and p90RSK and also via p38 MAP Kinase and MSK1. CREB exhibit deficiencies in spatial learning tasks, while flies overexpressing or lacking CREB show enhanced or diminished learning, respectively.。