title: AKT induces erythroid-cell maturation of JAK2-deficient fetal liver progenitor cells and is required for Epo regulation of erythroid-cell differentiation.
abstract: AKT serine threonine kinase of the protein kinase B (PKB) family plays essential roles in cell survival, growth, metabolism, and differentiation. In the erythroid system, AKT is known to be rapidly phosphorylated and activated in response to erythropoietin (Epo) engagement of Epo receptor (EpoR) and to sustain survival signals in cultured erythroid cells. Here we demonstrate that activated AKT complements EpoR signaling and supports erythroid-cell differentiation in wild-type and JAK2-deficient fetal liver cells. We show that erythroid maturation of AKT-transduced cells is not solely dependent on AKT-induced cell survival or proliferation signals, suggesting that AKT transduces also a differentiation-specific signal downstream of EpoR in erythroid cells. Down-regulation of expression of AKT kinase by RNA interference, or AKT activity by expression of dominant negative forms, inhibits significantly fetal liver-derived erythroid-cell colony formation and gene expression, demonstrating that AKT is required for Epo regulation of erythroid-cell maturation.
authors.affiliation: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. saghi.ghaffari@mssm.edu
authors.forename: Saghi
authors.initials: S
authors.lastname: Ghaffari
authors.forename: Claire
authors.initials: C
authors.lastname: Kitidis
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Dragan
authors.initials: D
authors.lastname: Marinkovic
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
authors.forename: Biao
authors.initials: B
authors.lastname: Luo
authors.forename: Joseph
authors.initials: J
authors.lastname: Marszalek
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000502:physiology*; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology; D005333:Fetus / Q000166:cytology / Q000502:physiology*; D053614:Janus Kinase 2; D008099:Liver / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D011518:Proto-Oncogene Proteins; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt