TPOisa68-85kDglycoproteinthatsignificantlyexpandsbonemarrowandsplenicmegakaryocytesandtheirCD34+precursors,resultinginincreasedplateletproduction.TPOsupportsearlymegakaryocyte-ProgenitorcolonyformationandinducesexpressionofmegakaryocytedifferentiationMarkers,polyploidization,andmaturationintoplatelets.Encodedbytheproto-oncogenec-Mpl,theTPOreceptorc-MpllacksintrinsickinasedomainsbutTPObindingcharacteristicallyinducestyrosinephosphorylationofmultipleintracellularproteins.TheJanusfamilyofnon-receptorproteintyrosinekinases(JAKs)isthekeymediatorofTPOreceptorsignaling.TheN-terminalfirst153aminoacidsofTPOcontainstheentirereceptor-bindingregion,whileitsC-terminaldomainhasmulti-N-linkedglycosylationsitesandfunctionstopromoteTPOsecretionandprolongitscirculatorysurvival.TPOaffectstheentirethrombopoieticprocessandhasstrongereffectsinthelaterstages.Otherthrombopoieticcytokinesincludestemcellfactor(SCF),IL-3,IL-6,andIL-11.ThereisgreattherapeuticpotentialforTPOforthetreatmentofmanyclinicalconditionsthatresultinthrombocytopenia.Human,mouseanddogTPOshow69-75%aminoacidhomology.RecombinantHumanTPOACFisanon-glycosylatedprotein,containingthe174aminoacidsofthereceptorbindingdomain,withamolecularweightof18.6kDa(2-5).
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