·NGF(2004-8-·TGFbeta(2004-8-·(2004-8-·(2004-8-·ROS(2004-8-·Toll-Like受體(2004-8-·Toll-Like(2004-8-·actin(2004-8-·Wnt/LRP6(2004-8-·WNT(2004-8-·WestNile西尼羅河(2004-8-·VitaminCC(2004-8-·(2004-8-·VEGF(2004-8-·TSP-1(2004-8-·Trka(2004-8-·dbpbmRNA(2004-8-·CARM1(2004-8-·CREB(2004-8-·TPO(2004-8-·Toll-Like(2004-8-·TNFR2(2004-8-·TNFR1(2004-8-·TNF/Stress(2004-8-·IGF-1(2004-8-·(2004-8-·Th1/Th2(2004-8-·TGFbeta(2004-8-·(2004-8-·TACIBCMAB(2004-8-·T(2004-8-·T(2004-8-·TCD3(2004-8-·Cardiolipin(2004-8-·Synaptic(2004-8-·HSP(2004-8-·Stat3(2004-8-·SREBP(2004-8-·(2004-8-·SonicHedgehogSHH)ptc1(2004-8-·SonicHedgehogShh)(2004-8-·SODD/TNFR1(2004-8-·AKT/mTOR(2004-8-·G(2004-8-·(2004-8-·IL1(2004-8-·acetyl從線粒體到胞漿過程(2004-8-·chemokine在T(2004-8-·SARS冠狀蛋白酶(2004-8-·Parkin在泛素-(2004-8-·nicotinicacetylcholine(2004-8-·(2004-8-·MEF2DT(2004-8-·Erk5(2004-8-·ERBB2(2004-8-·GPCRsEGF(2004-8-·BRCA1(2004-8-·Rho(2004-8-·Leptin(2004-8-·PML(2004-8-·p27(2004-8-·MAPK(2004-8-·(2004-8-·eIF4ep70S6(2004-8-·eIF2(2004-8-·plk3(2004-8-·BAD(2004-8-·Reelin(2004-8-·RBDNA(2004-8-·NK(2004-8-·Ras(2004-8-·Rac1(2004-8-·PTEN(2004-8-·notch(2004-8-·A（PKA）(2004-8-·Proteasome(2004-8-·Prion朊的信號通路(2004-8-·Presenilin在notchwnt(2004-8-·mRNA的poly(A)(2004-8-·(2004-8-·PKCmyosin(2004-8-·C（PLC）(2004-8-·PertussistoxinCCR5(2004-8-·Pelp1(2004-8-·PDGF(2004-8-·p53(2004-8-·p38MAPK(2004-8-·Nrf2是氧化應激基本表達的關鍵(2004-8-·OX40(2004-8-·hTerc(2004-8-·hTert(2004-8-·AIF(2004-8-·Omega(2004-8-·(2004-8-·NKNO2IL-12(2004-8-·TOR(2004-8-·NO(2004-8-·NF-kB(2004-8-·NFAT(2004-8-·(2004-8-·VIPPACAPT(2004-8-·(2004-8-·MAPK(2004-7-·(2004-7-·(2004-7-·MAPK級路(2004-7-·MAPK(2004-7-·BCR(2004-7-·(2004-7-·wnt(2004-7-·(2004-7-·G2/M(2004-7-·G1/S(2004-7-·Jak/STAT(2004-7-·TGFbeta(2004-7-·NFkappaB(2004-7-·p38MAPK(2004-7-·SAPK/JNK信號級路(2004-7-·GMAPK(2004-7-·MAPK(2004-7-·eif2(2004-7-·(2004-7-·(2004-7-(2004-7-·(2004-7-·(2004-7-·MAPK/ERK(2004-7-·MAPK(2004-7-·Pitx2多步調節轉錄(2004-7-·IGF-1RBAD(2004-7-·(2004-7-·mTOR(2004-7-·Msp/Ron(2004-7-·(2004-7-·線粒體毒堿轉移酶（CPT）系統(2004-7-·METS(2004-7-·Anandamide，內源性醇的代謝(2004-7-·黑色素細胞（Melanocyte）(2004-7-·DNA(2004-7-·(2004-7-·PPARa(2004-7-·對乙氨基酚（Acetaminophen）(2004-7-·mCalpain(2004-7-·MAPK(2004-7-·MAPKSMRT(2004-7-·(2004-7-·低密度脂蛋白（LDL）(2004-7-·LIS1在神經細胞的發育和遷移中的作用圖(2004-7-·Pyk2與Mapk相連的信號通路(2004-7-·galactose(2004-7-·Lectin(2004-7-·LckFynTCR(2004-7-·(2004-7-·Keratinocyte(2004-7-·(2004-7-·離子通道和佛波脂（PhorbalEsters）(2004-7-·Prothrombin(2004-7-·Ribosome(2004-7-·整合素（Integrin）(2004-7-·胰島素（Insulin）(2004-7-·Huntington(2004-7-·Gleevec(2004-7-·RasRhoG1/S(2004-7-·DR3，4，5(2004-7-·AKTGsk3(2004-7-·IL-7(2004-7-·IL22(2004-7-·IL-2T(2004-7-·IL12和Stat4TH1(2004-7-·IL-10(2004-7-·IL6(2004-7-·IL5(2004-7-·IL4(2004-7-·IL3(2004-7-·IL2(2004-7-·IL18(2004-7-·IL17(2004-7-·IGF-1(2004-7-·IFNgamma(2004-7-·INF(2004-7-·低氧誘導因子（HIF）(2004-7-·P53(2004-7-·人類巨細胞和MAP信號通路(2004-7-·(2004-7-·Howdoessalmonellahijackacell(2004-7-·Hop(2004-7-·HIV-INef:fasTNF(2004-7-·HIV-1(2004-7-·HIVT(2004-7-·(2004-7-·g-SecretaseErbB4(2004-7-·(2004-7-·GranzymeA(2004-7-·GTubby(2004-7-·(2004-7-·Ghrelin(2004-7-·PS1能產生beta(2004-7-·GATA3部分參與TH2細胞因子的表達(2004-7-·GABA(2004-7-·FXRLXR(2004-7-·SLRP(2004-7-·(2004-7-·FOSB(2004-7-·fMLP誘導趨化因子表達(2004-7-·Fibrinolysis(2004-7-·(2004-7-·FcEpsilonReceptorI(2004-7-·FAS(2004-7-·Prothrombin(2004-7-·真核細白質翻譯示意圖(2004-7-·雌激素反應蛋白EFP控制細胞的細胞周期(2004-7-·EPONF-kB(2004-7-·Erythrocyte(2004-7-·Erk1/Erk2Mapk(2004-7-·ErkPI-3K(2004-7-·(2004-7-·EPO(2004-7-·(2004-7-·NDK(2004-7-·(2004-7-·Eicosanoid(2004-7-·EGF(2004-7-分化的影響·E2F1(2004-7-·MTA-3在雌激素不敏感性中下調(2004-7-·雙鏈RNA誘導表達示意圖(2004-7-·Dicer信號通路（RNAi機理）(2004-7-·CDK5(2004-7-·TH1TH2(2004-7-·RARRXR(2004-7-·D4-GDI(2004-7-·(2004-7-·(2004-7-·CFTRbeta2(2004-7-·Cyclin(2004-7-·Ran(2004-7-·CyclinE(2004-7-·CXCR4(2004-7-·CTL(2004-7-·CTCF(2004-7-·(2004-7-·(2004-7-·VitD調控表達信號圖(2004-7-·(2004-7-·β(2004-7-·(2004-7-·(2004-7-·hSWI/SNFATP依賴的重塑(2004-7-·cAMPChREBP(2004-7-·(2004-7-·Ceramide(2004-7-·局部急染的細胞與分子信號(2004-7-·(2004-7-·G2/M(2004-7-·G1/S(2004-7-·CDK調節DNA(2004-7-·cdc25和chk1DNA(2004-7-·CD40L(2004-7-·CCR3(2004-7-·CBLEGF(2004-7-·3(2004-7-·2(2004-7-·(2004-7-·Catabolicpathwayforasparagineandasp(2004-7-·Caspase信號級路在細胞凋亡中的作用(2004-7-·CARM1(2004-7-·(2004-7-(2004-7-·DNA(2004-7-·Ca2+/CaM(2004-7-·B(2004-6-·BTG蛋白和細胞周期的調節(2004-6-·BRCA1(2004-6-·(2004-6-·BotulinumToxin(2004-6-·(2004-6-·Tryptophan(2004-6-·(2004-6-·sphingolipids(2004-6-·spermidinespermine(2004-6-·(2004-6-·(2004-6-·(2004-6-·(2004-6-·(2004-6-·(2004-6-·(2004-6-·Cysteine(2004-6-·Cysteine(2004-6-·Chorismate(2004-6-·Arginine(2004-6-·(2004-6-·β(2004-6-·BCR(2004-6-·SUMOylation(2004-6-·PPAR影響表達的基本信號機制圖(2004-6-·B(2004-6-·B(2004-6-·B(2004-6-·GPCR(2004-6-·ATM(2004-6-·(2004-6-·細胞凋亡信號調節DN段化(2004-6-·細胞凋亡DN段化與組織穩態的機理(2004-6-·反義核酸的作用機理---RNApolymeraseIII(2004-6-·(2004-6-·AntigenB(2004-6-·AnthraxToxinMechanismofAction(2004-6-·2(2004-6-·AngiotensinIIJNK(2004-6-·AlternativeComplementPathway(2004-6-·Alpha-synuclein和Parkin在怕病中的作用(2004-6-·ALK(2004-6-·AKT(2004-6-·AKAP95在有絲中的作用圖(2004-6-·Ahr(2004-6-·Agrin(2004-6-·ADP-Ribosylation(2004-6-·(2004-6-·AdhesionandDiapedesisofLymphocytes(2004-6-·AdhesionandDiapedesisofGranulocytes(2004-6-·(2004-6-·src(2004-6-·PKC與G(2004-6-·cAMPCSK抑制T(2004-6-·PKA(2004-6-·一氧化氮（NO）(2004-6-·RelA(2004-6-Mammaliancellmotilityrequiresactinpolymerizationinthedirectionofmovementtochangemembraneshapeandextendcytoplasmintolamellipodia.Thepolymerizationofactintodrivecellmovementalsoinvolvesbranchingofactinfilamentsintoanetworkorientedwiththegrowingendsofthefibersnearthecellmembrane.ManipulationofthisprocesshelpsbacterialikeSalmonellagainentryintocellstheyinfect.TwooftheproteinsinvolvedintheformationofYbranchesandincellmotilityareArp2andArp3,bothmembersofalargemultiproteincomplexcontainingseveralotherpolypeptidesaswell.TheArp2/3complexislocalizedattheYbranchjunctionandinducesactinpolymerization.Activityofthiscomplexisregulatedbymultipledifferentcellsurfacereceptorsignalingsystems,activatingWASP,andArp2/3inturntocausechangesincellshapeandcellmotility.WaspanditscousinWave-1interactwiththeArp2/3complexthroughthep21componentofthecomplex.ThecrystalstructureoftheArp2/3complexhasrevealedfurtherinsightsintothenatureofhowthecomplexworks.ActivationbyWave-1,anothermemberoftheWASPfamily,alsoinducesactinalterationsinresponsetoRac1signalsupstream.Wave-1isheldinaninactivecomplexinthecytosolthatisactivatedtoallowWave-1toassociatewithArp2/3.WhileWASPisactivatedbyinteractionwithCdc42,Wave-1,isactivatedbyinteractionwithRac1andNck.Wave-1activationbyRac1andNckreleasesWave-1withHspc300toactivateactinYbranchingandpolymerizationbyArp2/3.Differentmembersofthisgenefamilymayproducedifferentactincytoskeletalarchitectures.TheimmunologicaldefectsassociatedwithmutationoftheWASPgene,theWiskott-AldrichsyndromeforwhichWASPwasnamed,indicatestheimportanceofthissystemfornormalcellularfunction.CoryGO,RidleyAJ.Cellmotility:brakingWAVEs.Nature.2002Aug15;418(6899):732-3. Eden,S.,etal.(2002)MechanismofregulationofWAVE1-inducedactinnucleationbyRac1andNck.Nature418(6899),790-3FaletH,HoffmeisterKM,NeujahrR,HartwigJH.NormalArp2/3complexactivationinplaetslackingWASp.Blood.2002Sep15;100(6):2113-22.Kreishman-DeitrickM,RosenMK,Kreishman-DeltrickM.Ignitionofacellularmachine.NatCellBiol.2002Feb;4(2):E31-3.No Machesky,L.M.,Insall,R.H.(1998)Scar1andtherelatedWiskott-Aldrichsyndromeprotein,WASP,regulatetheactincytoskeletonthroughtheArp2/3complex.CurrBiol8(25),1347-56Robinson,R.C.etal.(2001)CrystalstructureofArp2/3complex.Science294(5547),1679-WeedsA,YeohS.Structure.ActionattheY-branch.Science.2001Nov23;294(5547):1660-1.NoWnt/LRP6Wntglycoproteinsplayaroleindiverseprocessesduringembryonicpatterninginmetazoathroughinteractionwithfrizzled-typeseven-transmembrane-receptors(Frz)tostabilizeb-catenin.LDL-receptor-relatedprotein6(LRP6),aWntco-receptor,isrequiredforthisinteraction.Dikkopf(dkk)proteinsarebothpositiveandnegativemodulatorsofthissignalingWNT信號轉WestNileWestNile (WNV)isamemberoftheFlaviviridae,aplus-stranded familythatincludesSt.Louis ,Kunjin ,yellowfever ,Dengue ,andJapaneseencephalitis .WNVwasinitiallyisolatedin1937intheWestNileregionofUgandaandhas eprevalentinAfrica,Asia,andEurope.WNVhasrapidlyspreadacrosstheUnitedStatesthroughitsinsecthostandcausesneurologicalsymptomsandencephalitis,whichcanresultinparalysisordeath.Since1999about3700casesofWestNile infectionand200deathshavebeenrecordedinUnitedStates.TheviralcapsidproteinlikelycontributestotheWNV-associateddeadlyinflammationviaapoptosisinducedthroughthemitochondrialpathway.WNVparticles(50nmmeter)consistofadensecore(viralproteinCencapsidated RNAgenome)surroundedbyamembraneenvelope(viralEandMproteinsembeddedinalipidbilayer).The bindstoaspecificcellsurfaceprotein(notyetidentified),aninteractionthoughttoinvolveEproteinwithhighlysulfatedneperansulfate(HSHS)residuesthatarepresentonthesurfacesofmanycellsandentersthecellbyaprocesssimilartothatofendocytosis.Onceinsidethecell,tomeRNAisreleasedintothecytoplasmviaendosomalrelease,afusionprocessinvolvingacidicpHinducedconformationchangeintheEprotein.TheRNAgenomeservesasmRNAandistranslatedbyribosomesintotenmatureviralproteinsareproducedviaproteolyticcleavage,whichincludethreestructuralcomponentsandsevendifferentnonstructuralcomponentsofthe .TheseproteinsassembleandtranscribecomplimentaryminusstrandRNAsfromtomicRNA.ThecomplimentaryminusstrandRNAinturnsservesastemplateforthesynthesisofpositive-strandedgenomicRNAs.OnceviralE,preMandCproteinshaveaccumulatedtosufficientlevel,theyassemblewiththegenomicRNAtoformprogenyvirions,whiigratetothecellsurfacewheretheyaresurroundedwithlipidenvelopandreleased.VitaminCCVitaminC(ascorbicacid)wasfirstidentifiedbyvirtueoftheessentialroleitplaysincollagenmodification,preventingthenutritionaldeficiencyscurvy.VitaminCactsasacofactorforhydroxylaseenzymesthatpost-translationallymodifycollagentoincreasethestrengthandelasticityoftissues.VitaminCreducesthemetalionprostheticgroupsofmanyenzymes,maintainingactivityofenzymes,alsoactsasananti-oxidant.AlthoughthepreventionofscurvythroughmodificationofcollagenmaybethemostobviousroleforvitaminC,itisnotnecessarilytheonlyroleofvitaminC.Svct1andSvct2areascorbatetransportersforvitaminCimportintotissuesandintocells.BothofthesetransportersspecificallytransportreducedL-ascorbicacidagainstaconcentrationgradientusingtheintracellularsodiumgradienttodriveascorbatetransport.Svct1isexpressedinepithelialcellsintheintestine,upregulatedincellularmodelsforintestinalepitheliumandappearstoberesponsiblefortheimportofdietaryvitaminCfromtheintestinallumen.ThevitaminCimportedfromtheintestineispresentinplasmaatapproximay50uM,almostexclusivelyinthereducedform,andistransportedtotissuestoplayavarietyofroles.Svct2importsreducedascorbatefromtheplasmaintoverydevelopmentofthelungsandbrainduringpregnancy.AhighconcentrationofvitaminCinneuronsofthedevelobrainmayhelpprotectthedevelobrainfromfreeradicaldamage.Theoxidizedformofascorbate,dehydroascorbicacid,istransportedintoavarietyofcellsbytheglucosetransporterGlut-1.Glut-1,Glut-3andGlut-4cantransportdehydroascorbate,butmaynottransportsignificanttiesofascorbicin

信息來源：本站 Thesignaltransductioncascaderesponsibleforsensinglightinvertebratesisoneofthebeststudiedsignaltransductionprocesses,andisinitiatedbyrhodopsininrodcells,amemberoftheG-proteincoupledreceptorgenefamily.RhodopsinremainstheonlyGPCRwhosestructurehasbeenresolvedathighresolution.Rhodopsininthediscsofrodcellscontainsabound11-cisretinalchromophore,asmallmoleculederivedfromVitaminAthtsastheligh cascade.Whenlightstrikes11-cisretinalandisabsorbed,itisomerizestoall-transretinal,changingtheshapeofthemoleculeandthereceptoritisboundto.Thischangeinrhodopsin抯shapealtersitsinteractionwithtransducin,thememberoftheG-proteingenefamilythatisspecificinitsroleinvisualsignaltransduction.ActivationoftransducincausesitsalphasubunittodissociatefromthetrimerandexchangeboundGDPforGTP,activatinginturnamembrane-boundcyclic-GMPspecificphosphodiesterasethathydrolyzescGMP.Intherestingrodcell,highlevelsofcGMPassociatewithacyclic-GMPgatedsodiumchannelintheplasmamembrane,keethechannelsopenandthemembraneoftherestingrodcellsdepolarized.Thisisdistinctfromsynapticgenerationofactionpotentials,inwhichstimulationinducesopeningofsodiumchannelsanddepolarization.WhencGMPgatedchannelsinrodcellsopen,bothsodiumandcalciumionsenterthecell,hyperpolarizingthemembraneandinitiatingtheelectrochemicalimpulseresponsibleforconveyingthesignalfromthesensoryneurontotheCNS.Therodcellintherestingstatereleaseshighlevelsoftheinhibitoryneurotransmitterglutamate,whilethereleaseofglutamateisrepressedbythehyperpolarizationinthepresenceoflighttotriggeradownstreamactionpotentialbyganglioncellsthatconveysignalstothebrain.ThecalciumwhichentersthecellalsoactivatesGCAP,whichactivatesguanylatecyclase(GC-1andGC-2)torapidlyproducemorecGMP,endingthehyperpolarizationandreturningthecelltoitsrestingdepolarizedstate.Aproteincalledrecoverinhelpsmediatetheinactivationofthesignaltransductioncascade,returningrhodopsintoitspreactivatedstate,alongwiththerhodopsinkinaseGrk1.PhosphorylationofrhodopsinbyGrklcausesarrestintobind,heltoterminatethereceptoractivationsignal.Dissociationandreassociationofretinal,dephosphorylationofrhodopsinandreleaseofarrestinallreturnrhodopsintoitsreadystate,preparedonceagaintorespondto

VEGF，低信息來源：本站 Vascularendothelialgrowthfactor(VEGF)playsakeyroleinphysiologicalbloodvesselformationandpathologicalangiogenesissuchastumorgrowthandischemicdiseases.HypoxiaisapotentinducerofVEGFinvitro.TheincreaseinsecretedbiologicallyactiveVEGFproteinfromcellsexposedtohypoxiaispartlybecauseofanincreasedtranscriptionrate,mediatedbybindingofhypoxia-induciblefactor-1(HIF1)toahypoxiaresponsiveelementinthe5'-flankingregionoftheVEGFgene.bHLH-PAStranscriptionfactorthatinteractswiththeAhreceptornucleartranslocator(Arnt),anditspredictedaminoacidsequenceexhibitssignificantsimilaritytothehypoxia-induciblefactor1alpha(HIF1a)product.HLFmRNAexpressioniscloselycorrelatedwiththatoforganssuggeststhatinanormoxicstate,HLFregulatesgeneexpressionofVEGF,variousglycolyticenzymes,andothersdrivenbytheHREsequence,andmaybeinvolvedindevelopmentofbloodvesselsandthesystemoflung.VEGFexpressionisdramaticallyinducedbyhypoxiadueinlargeparttoanincreaseinthestabilityofitsmRNA.HuRbindswithhighaffinityandspecificitytotheVRSelementthatregulatesVEGFmRNAstabilitybyhypoxia.Inaddition,aninternalribosomeentrysite(IRES)ensuresefficienttranslationofVEGFmRNAevenunderhypoxia.TheVHLtumorsuppressor(vonHippel-Lindau)regulatesalsoVEGFexpressionatapost-transcriptionallevel.ThesecretedVEGFisamajorangiogenicfactorthatregulatesmultipleendothelialcellfunctions,includingmitogenesis.CellularandcirculatinglevelsofVEGFareelevatedinhematologicmalignanciesandareadverselyassociatedwithprognosis.Angiogenesisisaverycomplex,tightlyregulated,multistepprocess,theingofwhiaywellproveusefulinthecreationofnoveltherapeuticagents.Currentapproachesbeinginvestigatedincludetheinhibitionofangiogenesisstimulants(e.g.,VEGF),ortheirreceptors,blockadeofendothelialcellactivation,inhibitionofmatrixmetalloproteinases,andinhibitionoftumorvasculature.Preclinical,phaseI,andphaseIIstudiesofbothmonoclonalantibodiestoVEGFandblockersoftheVEGFreceptortyrosinekinasepathwayindicatethattheseagentsaresafeandofferpotentialclinicalutilityinpatientswithhematologicmalignancies.TSP-1誘導細胞凋信息來源：本站 Astissuesgrowtheyrequireangiogenesistooccuriftheyaretobedwithbloodvesselsandsurvive.Factorsthatinhibitangiogenesismighta cancertherapeuticsbyblockingvesselformationintumorsandstarvingcancercells.Thrombospondin-1(TSP-1)isaproteinthatinhibitsangiogenesisandslowstumorgrowth,apparentlybyinducingapoptosisofmicrovascularendothelialcellsthatlinebloodvessels.TSP-1appearstoproducethisresponsebyactivatingasignalingpathwaythatbeginswithitsreceptorCD36atthecellsurfaceofthemicrovascularendothelialcell.Thenon-receptortyrosinekinasefynisactivatedbyTSP-1throughCD36,activatingtheapoptosisinducingproteaseslikecaspase-3andp38proteinkinases.p38isamitogen-activatedkinasethatalsoinducesapoptosisinsomeconditions,perhapsthroughAP-1activationandtheactivationofgenesthatleadto

Trka信息來源：本站 Nervegrowthfactor(NGF)isaneurotrophicfactorthatstimulatesneuronalsurvivalandgrowththroughTrkA,amemberofthetrkfamilyoftyrosinekinasereceptorsthatalsoincludesTrkBandTrkC.SomeNGFresponsesarealsomediatedormodifiedbyp75LNTR,alowaffinityneurotrophinreceptor.BindingofNGFtoTrkAstimulatesneuronalsurvival,andalsoproliferation.PathwayscoupledtotheseresponsesarelinkedtoTrkAthroughassociationofsignalingfactorswithspecificaminoacidsintheTrkAcytoplasmic.CellsurvivalthroughinhibitionofapoptosisissignaledthroughactivationofPI3-kinaseandAKT.Ras-mediatedsignalingandphospholipaseCbothactivatetheMAPkinasepathwaytostimulateproliferation.dbpb信息來源：本站 EndothelialcellsrespondtotreatmentwiththeproteasethrombinwithincreasedsecretionofthePDGFB-chain.ThisactivationoccursatthetranscriptionallevelandathrombinresponseelementwasidentifiedinthepromoterofthePDGFB-chaingene.AtranscriptionfactorcalledtheDNA-bindingproteinB(dbpB)mediatestheactivationofPDGFB-chaintranscriptioninresponsetothrombintreatment.DbpBisamemberoftheYboxfamilyoftranscriptionfactorsandbindstobothRNAandDNA.Intheabsenceofthrombin,endothelialcellscontaina50kDformofdbpBthatbindsRNAinthecytoplasmandmayplayaroleasachaperoneformRNA.The50kDversionofdbpBalsobindsDNAtoregulategenescontainingYboxelementsintheirpromoters.ThrombinactivationresultsinthecleavageofdbpBtoa30kDform.TheproteolyticcleavagereleasesdbpBfromRNAinthenucleus,allowingittoenterthenucleusandbindstoaregulatoryelementdistinctfromthesiterecognizedbythefulllength50kDdbpB.TesactivatedbycleaveddbpBincludethePDGFBchain.DephosphorylationofdbpBalsoregulatesnuclearentryandtranscriptionalbecloselyassociatedinacomplex.IdentificationoftheproteasethatcleavesdbpB,themechanismsofphosphorylationanddephosphorylation,andelucidationofthesignalingpathbywhichthrombininducesdbpBwillprovidegreaterunderstandingofthisnovelsignalingpathway.CARM1甲基信息來源：本站 Severalformsofpost-translationalmodificationregulateproteinactivities.Recently,proteinmethylationbyCARM1(coactivator-associatedargininemethyltransferase1)hasbeenobservedtoplayakeyroleintranscriptionalregulation.CARM1associateswiththep160classoftranscriptionalcoactivatorsinvolvedingeneactivationbysteroidhormonefamilyreceptors.CARM1alsointeractswithCBP/p300transcriptionalcoactivatorsinvolvedingeneactivationbyalargevarietyoftranscriptionfactors,includingsteroidhormonereceptorsandCEBP.OneofCARM1isthecorehistonesH3andH4,whicharealsosofthehistoneacetylaseactivityofCBP/p300coactivators.RecruitmentofCARM1tothepromoterregionbybindingtocoactivatorsincreaseshistonemethylationandmakespromoterregionsmoreaccessiblefortranscription.AnotherofCARM1methylationisacoactivatoritinteractswith,CBP.MethylationofCBPbyCARM1blocksCBPfromactingasacoactivatorforCREBandredirectsthelimitedCBPpoolinthecelltobeavailableforhormonereceptors.Otherformsofpost-translationalproteinmodificationsuchasphosphorylationarereversibleinnature,butasofyetaproteindemethylaseisnotknown.CREB轉錄因信息來源：本站 ThetranscriptionfactorCREBbindsthecyclicAMPresponseelement(CRE)andactivatestranscriptioninresponsetoavarietyofextracellularsignalsincludingneurotransmitters,hormones,membranedepolarization,andgrowthandneurotrophicfactors.ProteinkinaseAandthecalmodulin-dependentproteinkinasesCaMKIIstimulateCREBphosphorylationatSer133,akeyregulatorysitecontrollingtranscriptionalactivity.GrowthandneurotrophicfactorsalsostimulateCREBphosphorylationatSer133.PhosphorylationoccursatSer133viap44/42MAPKinaseandp90RSKandalsoviap38MAPKinaseandMSK1.CREBexhibitdeficienciesinspatiallearningtasks,whilefliesoverexpressingorlackingCREBshowenhancedordiminishedlearning,respectively.TPO信息來源：本站 Thrombopoietin(TPO)bindstoitsreceptorinducingaggregationandactivation.TPOsignalsitsgrowthregulatingeffectstothecellthroughseveralmajorpathwaysincludingMAPK(ERKandJNK),ProteinKinaseC,and

Toll-Like受信息來源：本站 Theinnateimmuneresponserespondsinageneralmannertofactorspresentininvadingpathogens.Bacterialfactorssuchaslipopolysaccharides(LPS,endotoxin),bacteriallipoproteins,peptidoglycansandalsoCpGnucleicacidsactivateinnateimmunityaswellasstimulatingthepecificimmuneresponseandtriggeringtheinflammatoryresponse.Membersofthetoll-likereceptor(TLR)genefamilyconveysignalsstimulatedbythesefactors,activatingsignaltransductionpathwaysthatresultintranscriptionalregulationandstimulateimmunefunction.TLR2isactivatedbybacteriallipoproteins,TLR4isactivatedbyLPS,andTLR9isactivatedbyCpGDNA;peptidoglycanrecognitionprotein(PGRP)isactivatedbypeptidoglycan(PGN).ThetheIL-1receptorassociatedkinase(IRAK)throughtheMyD88adaptorprotein,andsignalingthroughTRAF-6andproteinkinasecascadestoactivateNF-kBandJun.NF-kBandc-JunactivatetranscriptionofgenessuchastheproinflammatorycytokinesIL-1andIL-12.SeveralrecentreportshavesuggestedthatthefunctionalesofsignalingviaTLR2,TLR4andPGRParenotequivalent.Forexample,whiletheLPS-p38-dependentresponsewasdependentuponPU.1binding,thePGN-induced,p38responsewasnot.TheintracelularreceptorforPGN,PGRPisconservedfrominsectstomammals.Ininsects,PGRPactivatesprophenoloxidasecascade,apartoftheinsectantimicrobialdefensesystem.Becausemammalsdonothavetheprophenoloxidasecascade,itsfunctioninmammalsisunknown.However,itwassuggestedthatanidenticalproteinTag7wasatumornecrosisfactor-like(TNF-like)cytokine.PGRP/Tag7possessescytotoxicityandtriggersintranucleosomalDNAfragmentationincellsinthesamewayasmanyknownmembersoftheTNFfamily.FragmentationofDNAisoneofthecharacteristicsofapoptosis.Thepossibilitythatinanothersystem,PGRP/Tag7wouldinduceNF-kBactivation,asobservedforTRAIL(TNF-relatedapoptosis-inducingligand)receptorscanotberuledout.TNFR2信息來源：本站 TNFR2isthereceptorforthe171aminoacid19kDTNF(beta)(a.k.a.lymphotoxin).TNF(beta)isproducedbyactivatedlymphocytesandcanbecytotoxictomanytumorandothercells.Inneutrophils,endothelialcellsandosteoclastsTNF(beta)canleadtoactivationwhileinmanyothercelltypesitcanleadtoincreasedexpressionofMHCandadhesionmolecules.TNFR1信息來源：本站 TNFR1(a.k.a.p55,CD120a)isthereceptorforTNF(alpha)andalsowillbindTNF(beta).UponbindingTNF(alpha)aTNFR1+cellistriggeredtoundergoapoptosis.Thiscriticalregulatoryprocessis plishedbyactivatingtheproteolyticcaspasecascadethatresultsinthedegradationofmanycriticalcellularproteinsIGF-1受信息來源：本站TNF/Stress相關信信息來源：本站 TNFactsonseveraldifferentsignalingpathwaysthroughtwocellsurfacereceptors,TNFR1andTNFR2(SeeTNFR1andTNFR2SignalingPathways)toregulateapoptoticpathways,NF-kBactivationofinflammation,andactivatestress-activatedproteinkinases(SAPKs).InteractionofTNFR1withTRADDleadstoactivationofNF-kBandapoptosispathways,whileinteractionwithTRAF2hasgenerallybeenthoughttobeinvolvedinstresskinaseandNF-kBactivationbutisnotrequiredforTNFtoinduceapoptosis.ActivationofNF-kBismediatedbyTRAF2throughtheNIKkinaseandalsobyRIPbuttheobservationthatTNFactivatesNF-kBinmicelackingTRAF2indicatesthatTRAF-2doesnotplayanessentialroleinthisprocess.Stress-activatedproteinkinases,alsocalledJNKs,areafamilyofmapkinasesactivatedbycellularstressandinflammatorysignals.BindingofTNFtotheTNFR1receptoractivatesthegerminalcenterkinase(GCK)throughtheTNFadaptorTraf2,activatingthemapkinaseMEKK1.BothGCKandMEKK1interactwithTraf2,andGCKisrequiredforMEKK1activationbyTNF,butGCKkinaseactivitydoesnotappeartoberequiredforMEKK1activation.Instead,GCKactivatesMEKK1bycausingMEKK1oligomerizationandautophosphorylation.increasestheaffinityofTraf2forGCKtoincreaseMapkinaseactivationbyTNF.Onceactivated,MEKK1standsatthetopofamapkinasepathwaysleadingtotranscriptionalregulation,includingJNKphosphorylationofc-JuntostimulatetranscriptionalactivationbyAP-1,aheterodimerofc-junandfosorATFproteins.Theactivationofthep38MapkinasealsocontributestoAP-1activationleadingtothetranscriptionalactivationofmanystressandgrowthrelatedgenes.RIPhasbeensuggestedasacomponentofthep38pathwayinadditiontoplayingaroleinNF-kBactivation.MEKK1knockoutmicesupporttheroleofMEKK1inJNKactivationinsomecellsbutdidnotsupportMEKK1dependentactivationofNF-kB.AlternativeredundantmechanismsmayobscuretheroleofMEKK1inNF-kBmechanisms.TNFactivationofstresskinasepathwaysanddownstreamtranscriptionfactorsmayhelptomodulatetheapoptoticpathwaysalsoactivatedbyTNF.共刺激信信息來源：本站 ForaTcelltobeactivatedbyaspecificantigen,theTcellreceptormustrecognizecomplexesofMHCIwiththeantigenonthesurfaceofanantigen-presentingcell.TcellsandtheTcellreceptorcomplexdonotrespondtoantigeninsolution,butevenforthespecificantigentheyonlyrespondtoantigen-MHC-1complexesonthecellsurface.ThisinteractionisnecessaryforTcellactivation,butitisnotsufficient.Tcellactivationalsorequiresaco-stimulatorysignalinvolvinginteractionofCD28ontheTcellwithCD80orCD86(B7familygenes)ontheantigen-presentingcell.CD28activatesasignaltransductionpathwayactingthroughPI-3K,LckandGrb-2/ITKtoprovideitsco-stimulatorysignalforTcellactivation.AnothermeanstocontrolTcellactivationisbyexpressingfactorsthatdown-regulateTcellactivation.SignalingbyactivatedTcellreceptorsinducesexpressionofCTLA-4,areceptorthatopposesTcellactivation.CTLA-4hasahigheraffinitythanCD28forB7proteins,terminatingTcellactivation.ICOSisaproteinrelatedtoCD28thatisonlyexpressedonactivatedTcells,andthatprovidesanotherimportantco-stimulatorysignal.Therequirementforco-stimulatorysignalsprovidesadditionalcontrolmechanismsthatpreventinappropriateandhazardousTcellTh1/Th2信息來源：本站 HelperTcellsarefoundintwodistinctcelltypes,Th1andTh2distinguishedbyt