
Cataloguenumber
CYT-074
Synonyms
Introduction
Description
Source
PhysicalAppearance
Formulation
StABIlity
Purity
Aminoacidsequence
SafetyDataSheet
SDS
Usage
Background
ThisfactorwasfoundintheconditionedmediumofthehumanneuroepitheliomacelllineSHEP1andthemousemyoblastcelllineC2C12ras.TheCDNAencodingaproteinof498aminoacidswasisolatedbyusingasecretion-trapexpressioncloningprocedureexploitingthepresenceofasignalsequencepresentingrowthfactorsthataresecretedbyproducercells(Davisetal,1996).Murineandhumanfactorsshow97%identityattheaminoacidlevel.Forarelatedfactorsee:CDT6.Thehumangenehasbeenmappedtochromosome8q22.3-q23(Cheungetal,1998).
Theexpressionofangiopoietin-1mRNAisdownregulatedbyPDGF,EGF,IL1-beta,andTGF-beta(Enholmetal,1997).
Angiopoietin-1isaligandforthereceptor-liketyrosinekinasedesignatedTIE-2(Davisetal,1996).BindingofAngiopoietin-1toitsreceptorinducestyrosinephosphorylationofthecytoplasmicreceptordomain.AnaturallyoccuringantagoNISTofAngiopoietin-1bindingtoTIE-2isAngiopoietin-2.Angiopoietin-1alsobindstotheTIE-1receptorandthisinteractionappearstobecriticalforthedevelopmentoftheright-handsidevenoussystem.Itisdispensablefortheleft-handsidevenoussystem,suggestingthatright-handandleft-handsidevascularnetworksareestablishedearlybeforeasymmetricalfeaturesofthenetworkbecomemorphologicallydiscernIBLeLoughnaandSato,2001).
Angiopoietin-1doesnotdirectlypromotethegrowthofculturedendothelialcells.Angiopoietin-1ischemotacticforendothelialcells(Witzenbichleretal,1998).ExcesssolubleTIE-2receptorsabolishthechemotacticresponseofendothelialcellstowardangiopoietin-1.Angiopoietin-1hasbeenshowntocounteractcelldeathbyapoptosisinculturedendothelialcells(Holashetal,1999).Angiopoietin-1alsoactsasanapoptosissurvivalfactorforendothelialcellsandthiseffectisaugmentedbythepresenceofVEGF(Kwaketal,1999).
Angiopoietin-2dose-dependentlyblocksdirectedmigrationtowardAngiopoietin-1.Carlsonetal(2001)haveshownthatAng-1bindsratherselectivelytovitronectinandthatAng-1candirectlysupportadhesionofhumanumbilicalveinendothelialcellsandfibroblastsinaprocessmediatedbyintegrins.
ThephysiologicrolesofAngiopoietin-1anditsreceptorarelimitedtoangiogenicprocessesthatoccursubsequenttotheearliervasculogenicandangiogenicactionsoftheVEGFfamilyandtheirreceptors.However,itisunlikemostoftheknownangiogenesisfactorssuchasVEGFandotherclassicalendothelialcellgrowthfactorsinthatadditionofthefactortoculturesofendothelialcellsdoesnotdirectlypromotecellgrowtheventhoughtheTIE-2receptorbecomesactivated.Angiopoietin-1alsoappearstobeincapableofinducingtheformationoftubulesbyendothelialcells.
Angiopoietinscanpotentiatetheeffectsofotherangiogeniccytokines.AninvestigationoftheimpactofangiopoietinsonneovascularizationinvivointhecorneamicropocketassayofneovascularizationdemonstratesthatneitherAngiopoietin-1norAngiopoietin-2alonepromoteneovascularization.Holashetal(1999)haveshownthatasubsetoftumorsinitiallygrowsbycooptingexistinghostvessels.RegressionofthesevesselsviaaprocessthatinvolvesdisruptionofinteractionsbetweenendothelialcellsandsmoothmusclecellsaswellascelldeathbyapoptosisofendothelialcellsfirstcauseslossoftumourcellsbeforeangiogenesisbeginsatthetumormarginandthetumorisrescuedundertheinfluenceofVEGF,Angiopoietin-1,andprobablyotherangiogenicstimuli.
TheembryonicexpressionpatternofAngiopoietin-1suggeststhatitplaysaparticularlyimportantroleinthedevelopingheart.Angiopoietin-1isexpressedhighlyinthemyocardialwallsurroundingtheendocardiumexpressingTIE-2.ExpressionofAngiopoietin-1becomesmuchmorewidespreadlaterindevelopment.