细胞常见信号通路图片合集.doc

目录actin肌丝5Wnt/LRP6信号7WNT信号转导7WestNile西尼罗河病毒8VitaminC维生素C在大脑中的作用10视觉信号转导11VEGF，低氧13TSP-1诱导细胞凋亡15Trka信号转导16dbpb调节mRNA17CARM1甲基化19CREB转录因子20TPO信号通路21Toll-Like受体22TNFR2信号通路24TNFR1信号通路25IGF-1受体26TNF/Stress相关信号27共刺激信号29Th1/Th2细胞分化30TGFbeta信号转导32端粒、端粒酶与衰老33TACI和BCMA调节B细胞免疫35T辅助细胞的表面受体36T细胞受体信号通路37T细胞受体和CD3复合物38Cardiolipin的合成40Synaptic突触连接中的蛋白42HSP在应激中的调节的作用43Stat3信号通路45SREBP控制脂质合成46酪氨酸激酶的调节48SonicHedgehog(SHH)受体ptc1调节细胞周期51SonicHedgehog(Shh)信号53SODD/TNFR1信号56AKT/mTOR在骨骼肌肥大中的作用58G蛋白信号转导59IL1受体信号转导60acetyl从线粒体到胞浆过程62趋化因子chemokine在T细胞极化中的选择性表达63SARS冠状病毒蛋白酶65SARS冠状病毒蛋白酶67Parkin在泛素-蛋白酶体中的作用69nicotinicacetylcholine受体在凋亡中的作用71线粒体在细胞凋亡中的作用73MEF2D在T细胞凋亡中的作用74Erk5和神经元生存75ERBB2信号转导77GPCRs调节EGF受体78BRCA1调节肿瘤敏感性79Rho细胞运动的信号81Leptin能逆转胰岛素抵抗82转录因子DREAM调节疼敏感84PML调节转录86p27调节细胞周期88MAPK信号调节89细胞因子调节造血细胞分化91eIF4e和p70S6激酶调节92eIF2调节93谷氨酸受体调节ck1/cdk594BAD磷酸化调节95plk3在细胞周期中的作用96Reelin信号通路97RB肿瘤抑制和DNA破坏98NK细胞介导的细胞毒作用99Ras信号通路100Rac1细胞运动信号101PTEN依赖的细胞生长抑制和细胞凋亡103蛋白激酶A（PKA）在中心粒中的作用104notch信号通路106蛋白酶体Proteasome复合物108Prion朊病毒的信号通路109早老素Presenilin在notch和wnt信号中的作用110淀粉样蛋白前体信号112mRNA的poly(A)形成113PKC抑制myosin磷酸化114磷脂酶C（PLC）信号115巨噬细胞Pertussistoxin不敏感的CCR5信号通路116Pelp1调节雌激素受体的活性117PDGF信号通路118p53信号通路120p38MAPK信号通路121Nrf2是氧化应激基本表达的关键基因122OX40信号通路123hTert转录因子的调节作用124hTerc转录调节活性图125AIF在细胞凋亡中的作用126Omega氧化通路127核受体在脂质代谢和毒性中的作用129NK细胞中NO2依赖的IL-12信号通路131TOR信号通路133NO信号通路134NF-kB信号转导通路135NFAT与心肌肥厚的示意图137神经营养素及其表面分子139神经肽VIP和PACAP防止活化T细胞凋亡图141神经生长因子信号图142细胞凋亡信号通路144MAPK级联通路144MAPK信号通路图145BCR信号通路146蛋白质乙酰化示意图147wnt信号通路148胰岛素受体信号通路149细胞周期在G2/M期的调控机理图151细胞周期G1/S检查点调控机理图152Jak-STAT关系总表153Jak/STAT信号155TGFbeta信号156NFkappaB信号157p38MAPK信号通路159SAPK/JNK信号级联通路160从G蛋白偶联受体到MAPK161MAPK pathwayMAPK级联信号图162eIF-4E和p70S6激酶调控蛋白质翻译163eif2蛋白质翻译164蛋白质翻译示意图165线粒体凋亡通路167死亡受体信号通路168凋亡抑制通路170细胞凋亡综合示意图171Akt/Pkb信号通路172MAPK/ERK信号通路174哺乳动物MAPK信号通路175Pitx2多步调节基因转录176IGF-1R导致BAD磷酸化的多个凋亡路径177多重耐药因子179mTOR信号通路180Msp/Ron受体信号通路181单核细胞和其表面分子182线粒体的肉毒碱转移酶（CPT）系统183METS影响巨噬细胞的分化184Anandamide，内源性大麻醇的代谢186黑色素细胞（Melanocyte）发育和信号187DNA甲基化导致转录抑制的机理图188蛋白质的核输入信号图190PPARa调节过氧化物酶体的增殖192对乙氨基酚（Acetaminophen）的活性和毒性机理194mCalpain在细胞运动中的作用196MAPK信号图198MAPK抑制SMRT活化200苹果酸和天门冬酸间的转化201低密度脂蛋白（LDL）在动脉粥样硬化中的作用202LIS1基因在神经细胞的发育和迁移中的作用图204Pyk2与Mapk相连的信号通路205galactose代谢通路206Lectin诱导补体的通路207Lck和Fyn在TCR活化中的作用208乳酸合成图209Keratinocyte分化图210离子通道在心血管内皮细胞中的作用211离子通道和佛波脂（PhorbalEsters）信号213内源性Prothrombin激活通路214Ribosome内化通路216整合素（Integrin）信号通路217胰岛素（Insulin）信号通路218MatrixMetalloproteinases219组氨酸去乙酰化抑制剂抑制Huntington病220Gleevec诱导细胞增殖222Ras和Rho在细胞周期的G1/S转换中的作用224DR3，4，5受体诱导细胞凋亡225AKT调控Gsk3图226IL-7信号转导227IL22可溶性受体信号转导图229IL-2活化T细胞图230IL12和Stat4依赖的TH1细胞发育信号通路232IL-10信号通路233IL6信号通路234IL5信号通路236actin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), 790-3 Falet 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), 1679-84 Weeds 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WestNile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 the WNV-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. Once inside 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.VitaminC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 in rhodopsin抯 shape alters its interaction with transducin, the member of the G-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 the VEGF 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 a post-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 rel