常见信号通路

抗氧化相关的信号通路抗氧化相关的信号通路可以包括以下几个重要的途径：1. NF-κB通路：核因子-κB（NF-κB）是一种转录因子，通过调节大量抗氧化相关基因的表达，参与调控氧化应激反应。

在正常情况下，NF-κB处于细胞质中，并与其抑制剂IκB结合形成复合物。

在反应性氧化物的刺激下，IκB蛋白被降解，使NF-κB释放并进入细胞核，激活相关的抗氧化基因。

2. Nrf2通路：核因子相关因子2（Nrf2）是一种转录因子，它可以直接结合到抗氧化响应元素（ARE）启动子区域，激活抗氧化酶的转录。

在正常情况下，Nrf2位于细胞质中，并通过结合其抑制剂Keap1而被静止。

然而，当细胞处于氧化应激或电子接受者的激活状态时，Nrf2从Keap1中解离，并进入细胞核，激活抗氧化酶的基因表达。

3. PI3K/Akt通路：磷脂酰肌醇3激酶（PI3K）/蛋白激酶B （Akt）通路在细胞中起着重要的生存信号传导作用。

Akt的活化可以通过多种途径增强细胞的抗氧化能力。

一方面，Akt 可以通过抑制FOXO转录因子的活性，减少抗氧化相关的基因的表达。

另一方面，Akt可以通过激活Nrf2通路来增加抗氧化基因的转录。

4. MAPK通路：线粒体抗氧化酶基因的表达往往受到线粒体孤儿受体的调节，比如P53和Nrf2。

这些线粒体孤儿受体的活性可以通过线粒体糖代谢相关激酶（AMPK）和线粒体PERK/eIF2α通路中线粒体rhodanase的活性调控来维持。

而这些通路的活化往往依赖于线粒体抗氧化酶基因的表达。

以上是几个比较典型的抗氧化相关信号通路，这些通路在细胞中的正常运行和平衡对于维持细胞的抗氧化平衡和防止过氧化损伤非常重要。

细胞生物学信号通路,是指细胞对外界信号作出的反应，并将其传递至其他细胞或组织的过程。

以下是一些常见的细胞生物学信号通路：
1.MAPK信号通路：该通路是介导细胞增殖和分化的主要途径。

当细胞受到生长因子或其它外部刺激时，MAPK信号通路会被激活，引发一系列的信号传递事件，最终导致细胞增殖或分化。

2.PI3K信号通路：该通路是介导细胞生长、增殖和存活的重要途径。

当细胞受到生长因子或其它外部刺激时，PI3K信号通路会被激活，产生磷酸化的磷脂酰肌醇，从而触发一系列的信号传递事件，最终导致细胞生长、增殖或存活。

3.Notch信号通路：该通路是介导细胞分化、发育和凋亡的重要途径。

当Notch受体与配体结合时，Notch信号通路会被激活，产生一系列的信号传递事件，最终导致细胞分化、发育或凋亡。

4.Wnt信号通路：该通路是介导细胞增殖和凋亡的重要途径。

当Wnt受体与配体结合时，Wnt信号通路会被激活，产生一系列的信号传递事件，最终导致细胞增殖或凋亡。

5.TGF-β信号通路：该通路是介导细胞分化、凋亡和细胞外基质重塑的重要途径。

当TGF-β受体与配体结合时，TGF-β信号通路会被激活，产生一系列的信号传递事件，最终导致细胞分化、凋亡或细胞外基质重塑。

这些信号通路在细胞生命活动中发挥着至关重要的作用，参与了细胞的多种生理和病理过程。

信号通路的符号
信号通路是指细胞内或细胞间的一系列分子相互作用，从而将外部信号转化为细胞内的生物学反应。

在信号通路中，各种分子通过特定的相互作用形成一个复杂的网络，这些分子通常用符号来表示。

一些常见的信号通路符号包括：
1. 受体（Receptor）：细胞表面或细胞内的分子，能够识别并结合外部信号分子。

2. 配体（Ligand）：能够与受体结合的外部信号分子。

3. 激酶（Kinase）：能够将磷酸基团转移到其他分子上的酶。

4. 磷酸化（Phosphorylation）：激酶将磷酸基团加到其他分子上的过程。

5. 蛋白质（Protein）：执行细胞功能的大分子。

6. 第二信使（Second Messenger）：细胞内的小分子，如cAMP、cGMP、Ca2+等，能够传递信号并引发细胞反应。

7. 转录因子（Transcription Factor）：能够调节基因转录的蛋白质。

这些符号在信号通路的示意图中经常使用，帮助我们理解信号分子之间的相互作用和信号传递的过程。

完整的信号通路阐释信号通路是指在生物学或工程学领域中，传递信号的一系列分子或电气元件之间的路径或通路。

在不同的领域，信号通路的概念可能有所不同，下面将对生物学和电子工程领域中的信号通路进行阐释。

### 生物学领域的信号通路：在细胞生物学中，信号通路是一系列的生物分子相互作用，以调控细胞的生理功能和生物学行为。

以下是一个典型的细胞信号通路的阐释：1. 信号发起：通常由外部刺激引发，例如细胞外的激素、生长因子或环境因子。

2. 受体激活：外部信号被细胞表面的受体捕获和识别，这可能是膜受体或细胞内受体。

3. 传递：受体激活后，内部的信号分子会传递信号，通常通过一系列蛋白质激酶、磷酸化等过程。

4. 放大：信号通过引发级联反应，逐渐放大，确保在细胞内产生足够的响应。

5. 传导：放大后的信号被传导至细胞内的执行器，可能是转录因子、酶或其他调节分子。

6. 细胞响应：最终，信号通路的活动导致细胞产生一定的生物学响应，如基因表达的改变、细胞运动、增殖或凋亡等。

7. 负反馈：为了维持细胞内稳态，通常信号通路还包含负反馈机制，以避免过度激活。

### 电子工程领域的信号通路：在电子工程中，信号通路是指信号从输入端经过一系列电子元件传递到输出端的路径。

以下是一个简单的电子信号通路的阐释：1. 信号源：通常是传感器或其他设备，产生需要处理的电信号。

2. 输入端：信号进入信号通路的起始点。

3. 处理元件：信号通过一系列的电阻、电容、电感、运算放大器等元件进行处理，可能会经过滤波、放大或调制等过程。

4. 传输：处理后的信号通过导线或电路板传输到下一个阶段。

5. 输出端：处理后的信号最终到达输出端，可以是用于显示、记录、控制其他设备等。

6. 反馈：反馈机制可以根据输出来调整输入，以便维持系统的稳定性和性能。

这只是两个领域中信号通路的简单阐释，实际上，不同的领域和应用场景中的信号通路可能会更加复杂和多样化。

细胞的4类8种信号通路
细胞的信号通路主要包括以下四种类型：
1. GPCR-cAMP-PKA 和 RTK-Ras-MAPK 信号通路：通过活化受体导致胞质蛋白激酶的活化，活化的胞质蛋白激酶转位到核内并磷酸化特异的核内转录因子，进而调控基因转录。

2. TGF-β-smad和JAK-STAT信号通路：通过配体与受体结合激活受体本身或偶联激酶的活性，然后直接或间接导致胞质内特殊转录因子的活化，进而影响核内基因的表达。

3. Wnt受体和Hedgehog受体介导的信号通路：通过配体与受体结合引发胞质内多蛋白复合物去装配，从而释放转录因子，转录因子再转位到核内调控基因表达。

4. NF-κB和Notch信号通路：通过抑制物或受体本身的蛋白切割作用，释放活化的转录因子，转录因子再转位到核内调控基因表达。

信号通路及传递方式信号通路是指在电子设备或系统中传输、处理和转换信号的路径。

传递方式是指信号在信号通路中的传输方式。

下面将分别对信号通路和传递方式进行详细介绍。

一、信号通路1.信号通路的基本概念信号通路是指在电子设备或系统中传输、处理和转换信号的路径。

在信号通路中，信号可以通过不同的元件、器件和电路进行传输和处理，比如放大器、滤波器、混频器等。

信号通路的设计和构建是电子系统设计的基础，它直接影响信号传输的质量和系统性能。

2.信号通路的组成部分信号通路通常由以下几个组成部分构成：(1)信号源：信号源是指产生和提供输入信号的元件或器件，可以是传感器、发电机、麦克风等。

(2)信号处理器：信号处理器对输入信号进行处理和转换，比如放大、滤波、混频、调制等。

常用的信号处理器有放大器、滤波器、混频器、调制器等。

(3)信号传输线：信号传输线用于将处理后的信号从一个地方传输到另一个地方，可以是电线、光纤等。

(4)信号接收器：信号接收器用于接收传输线上传输的信号，并将其转换为需要的形式，如数字信号转换为模拟信号。

3.信号通路的分类根据信号的性质和传输方式的不同，信号通路可以分为以下几类：(1)模拟信号通路：模拟信号通路用于处理和传输模拟信号，模拟信号是连续变化的信号，它的值可以在无限范围内变化。

模拟信号通路常用于音频、视频和射频等应用领域。

(2)数字信号通路：数字信号通路用于处理和传输数字信号，数字信号是离散的信号，它的值只能取有限个数。

数字信号通路通常用于计算机、通信和显示设备等领域。

(3)模拟数字混合信号通路：模拟数字混合信号通路用于处理和传输模拟信号和数字信号的混合信号。

模拟数字混合信号通路常用于混合信号芯片、电视机、手机等设备中。

4.信号通路的设计与应用信号通路的设计需要考虑信号的频率、幅度、失真、噪声等因素。

设计一个良好的信号通路可以提高信号传输的质量和系统的性能。

信号通路的应用非常广泛，它被广泛应用于电子设备和系统中。

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.。

常见的几种信号通路1 JAK-STAT信号通路1) JAK与STAT蛋白JAK—STAT信号通路是近年来发现的一条由细胞因子刺激的信号转导通路,参与细胞的增殖、分化、凋亡以及免疫调节等许多重要的生物学过程.与其它信号通路相比，这条信号通路的传递过程相对简单，它主要由三个成分组成，即酪氨酸激酶相关受体、酪氨酸激酶JAK 和转录因子STAT。

(1) 酪氨酸激酶相关受体（tyrosine kinase associated receptor)许多细胞因子和生长因子通过JAK—STAT信号通路来传导信号，这包括白介素2？7(IL-2?7)、GM-CSF（粒细胞/巨噬细胞集落刺激因子）、GH（生长激素）、EGF（表皮生长因子）、PDGF （血小板衍生因子）以及IFN（干扰素)等等。

这些细胞因子和生长因子在细胞膜上有相应的受体。

这些受体的共同特点是受体本身不具有激酶活性，但胞内段具有酪氨酸激酶JAK的结合位点。

受体与配体结合后，通过与之相结合的JAK的活化,来磷酸化各种靶蛋白的酪氨酸残基以实现信号从胞外到胞内的转递。

（2) 酪氨酸激酶JAK（Janus kinase）很多酪氨酸激酶都是细胞膜受体,它们统称为酪氨酸激酶受体（receptortyrosine kinase, RTK），而JAK却是一类非跨膜型的酪氨酸激酶。

JAK是英文Janus kinase 的缩写，Janus在罗马神话中是掌管开始和终结的两面神.之所以称为两面神激酶，是因为JAK既能磷酸化与其相结合的细胞因子受体，又能磷酸化多个含特定SH2结构域的信号分子。

JAK蛋白家族共包括4个成员：JAK1、JAK2、JAK3以及Tyk2，它们在结构上有7个JAK同源结构域（JAK homology domain, JH），其中JH1结构域为激酶区、JH2结构域是“假”激酶区、JH6和JH7是受体结合区域.（3）转录因子STAT（signal transducer and activator of transcription）STAT被称为“信号转导子和转录激活子"。