| Immunogen | KLH-conjugatedlinearpeptidecorrespondingtohumanAkt1phosphorylatedatTyr326. |
| Epitope | PhosphorylatedTyr326 |
| Concentration | PleaserefertotheCertificateofAnalysisforthelot-specificconcentration. |
| Host | Rabbit |
| Specificity | ThisantibodyrecognizesAkt1phosphorylatedatTyr326. |
| SpeciesReactivity | - Human
- Mouse
- Rat
- Canine
- Xenopus
|
| SpeciesReactivityNote | DemonstratedtoreactwithHuman.PredictedtoreactwithMouse,Rat,Canine,andXenopusbasedon100%sequencehomology. |
| AntibodyType | PolyclonalAntibody |
| EntrezGeneNumber | |
| EntrezGeneSummary | Theserine-threonineproteinkinaseencodedbytheAKT1geneiscatalyticallyinactiveinserum-starvedprimaryandimmortalizedfibroblasts.AKT1andtherelatedAKT2areactivatedbyplatelet-derivedgrowthfactor.Theactivationisrapidandspecific,anditisabrogatedbymutationsinthepleckstrinhomologydomainofAKT1.Itwasshownthattheactivationoccursthroughphosphatidylinositol3-kinase.InthedevelopingnervoussystemAKTisacriticalmediatorofgrowthfactor-inducedneuronalsurvival.Survivalfactorscansuppressapoptosisinatranscription-independentmannerbyactivatingtheserine/threoninekinaseAKT1,whichthenphosphorylatesandinactivatescomponentsoftheapoptoticmachinery.Multiplealternativelysplicedtranscriptvariantshavebeenfoundforthisgene.[providedbyRefSeq]. |
| GeneSymbol | |
| Modifications | |
| PurificationMethod | AffinityPurfied |
| UniProtNumber | |
| UniProtSummary | FUNCTION:PlaysaroleasakeymodulatoroftheAKT-mTORsignalingpathwaycontrollingthetempooftheprocessofnewbornneuronsintegrationduringadultneurogenesis,includingcorrectneuronpositioning,dendriticdevelopmentandsynapseformation(Bysimilarity).Generalproteinkinasecapableofphosphorylatingseveralknownproteins.PhosphorylatesTBC1D4.Signalsdownstreamofphosphatidylinositol3-kinase(PI3K)tomediatetheeffectsofvariousgrowthfactorssuchasplatelet-derivedgrowthfactor(PDGF),epidermalgrowthfactor(EGF),insulinandinsulin-likegrowthfactorI(IGF-I).Playsaroleinglucosetransportbymediatinginsulin-inducedtranslocationoftheGLUT4glucosetransportertothecellsurface.MediatestheantiapoptoticeffectsofIGF-I.Mediatesinsulin-stimulatedproteinsynthesisbyphosphorylatingTSC2at"Ser-939"and"Thr-1462",therebyactivatingmTORC1signalingandleADIngtobothphosphorylationof4E-BP1andinactivationofRPS6KB1.Promotesglycogensynthesisbymediatingtheinsulin-inducedactivationofglycogensynthase.TheactivatedformcansuppressFoxOgenetranscriptionandpromotecellcycleprogression.EssentialfortheSPATA13-mediatedregulationofcellmigrationandadhesionassemblyanddisassembly.Ref.6Ref.10Ref.14Ref.15Ref.17Ref.19CATALYTICACTIVITY:ATP+aprotein=ADP+aphosphoprotein.
ENZYMEREGULATION:Threespecificsites,oneinthekinasedomain(Thr-308)andthetwootheronesintheC-terminalregulatoryregion(Ser-473andTyr-474),needtobephosphorylatedforitsfullactivation.
SUBUNITSTRUCTURE:InteractswithAGAP2(isoform2,PIKE-A),theinteractionrequiresguaninenucleotidesandstimulatesthekinaseactivity.Interacts(viatheC-terminus)withCCDC88A(viaitsC-terminus)andTHEM4(viaitsC-terminus).InteractswithAKTIP.Interacts(viaPHdomain)withMTCP1,TCL1AANDTCL1B.InteractswithTRAF6.InteractswithGRB10;theinteractionleadstoGRB10phosphorylationthuspromotingYWHAEbinding.InteractswithRARA;theinteractionphosphorylatesRARAandrepressesitstransactivationactivity.InteractswithTNK2.
SUBCELLULARLOCATION:Cytoplasm.Nucleus.Cellmembrane.Note:Nucleusafteractivationbyintegrin-linkedproteinkinase1(ILK1).NucleartranslocationisenhancedbyinteractionwithTCL1A.PhosphorylationonTyr-176byTNK2resultsinitslocalizationtothecellmembranewhereitistargetedforfurtherphosphorylationsonThr-308andSer-473leadingtoitsactivationandtheactivatedformtranslocatestothenucleus.
TISSUESPECIFICTY:Expressedinallhumancelltypessofaranalyzed.TheTyr-176phosphorylatedformshowsasignificantincreaseinexpressioninbreastcancersduringtheprogressivestagesi.e.normaltohyperplasia(ADH),ductalcarcinomainsitu(DCIS),invasiveductalcarcinoma(IDC)andlymphnodemetastatic(LNMM)stages.DOMAIN:BindingofthePHdomaintothephosphatidylinositol3-kinasealpha(PI3K)resultsinitstargetingtotheplasmamembrane.ThePHdomainmediatesinteractionwithTNK2andTyr-176isalsoessentialforthisinteraction.
TheAGC-kinaseC-terminalmediatesinteractionwithTHEM4.
PTM:PhosphorylationonThr-308,Ser-473andTyr-474isrequiredforfullactivity.ActivatedTNK2phosphorylatesitonTyr-176resultinginitsbindingtotheanionicplasmamembranephospholipidPA.Thisphosphorylatedformlocalizestothecellmembrane,whereitistargetedbyPDPK1andPDPK2forfurtherphosphorylationsonThr-308andSer-473leadingtoitsactivation.Ser-473phosphorylationbymTORC2favorsThr-308phosphorylationbyPDPK1.Ser-473phosphorylationisenhancedbyinteractionwithAGAP2isoform2(PIKE-A).Ser-473phosphorylationisenhancedinfocalcorticaldysplasiaswithTaylor-typeballooncells.
Ubiquitinated;undergoesboth"Lys-48"-and"Lys-63"-linkedpolyubiquitination.TRAF6-induced"Lys-63"-linkedAKT1ubiquitinationiscriticalforphosphorylationandactivation.Whenubiquitinated,ittranslocatestotheplasmamembrane,whereitbecomesphosphorylated.Whenfullyphosphorylatedandtranslocatedintothenucleus,undergoes"Lys-48"-polyubiquitinationcatalyzedbyTTC3,leadingtoitsdegradationbytheproteasome.Ref.10Ref.14Ref.17Ref.34Ref.8Ref.20Ref.9Ref.16Ref.21Ref.26Ref.27INVOLVEMENTINDISEASE:DefectsinAKT1areacauseofsusceptibilitytobreastcancer(BC)[MIM:114480].Acommonmalignancyoriginatingfrombreastepithelialtissue.Breastneoplasmscanbedistinguishedbytheirhistologicpattern.Invasiveductalcarcinomaisbyfarthemostcommontype.Breastcancerisetiologicallyandgeneticallyheterogeneous.Importantgeneticfactorshavebeenindicatedbyfamilialoccurrenceandbilateralinvolvement.Mutationsatmorethanonelocuscanbeinvolvedindifferentfamiliesoreveninthesamecase.
DefectsinAKT1areassociatedwithcolorectalcancer(CRC)[MIM:114500].
DefectsinAKT1areassociatedwithsusceptibilitytoovariancancer[MIM:604370];alsocalledsusceptibilitytofamilialbreast-ovariancancertype1(BROVCA1).
SEQUENCESIMILARITIES:Belongstotheproteinkinasesuperfamily.AGCSer/Thrproteinkinasefamily.RACsubfamily.
Contains1AGC-kinaseC-terminaldomain.
Contains1PHdomain.
Contains1proteinkinasedomain. |
| MolecularWeight | ~56kDaobserved |
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