title: Protein kinase C δ deficiency enhances megakaryopoiesis and recovery from thrombocytopenia.
abstract: OBJECTIVE
  We previously determined that protein kinase C δ (PKCδ) regulates platelet function. However, the function of PKCδ in megakaryopoiesis is unknown.
  
  
  RESULTS
  Using PKCδ(-/-) and wild-type littermate mice, we found that deficiency of PKCδ caused an increase in white blood cells and platelet counts, as well as in bone marrow and splenic megakaryocytes (P<0.05). Additionally, the megakaryocyte number and DNA content were enhanced in PKCδ(-/-) mouse bone marrow after culturing with exogenous thrombopoietin compared with wild-type (P<0.05). Importantly, thrombopoietin-induced signaling was also altered with PKCδ deletion because both extracellular signal-regulated kinase and Akt308 phosphorylation were heightened in PKCδ(-/-) megakaryocytes compared with wild-type. Finally, PKCδ(-/-) mice recovered faster and had a heightened rebound thrombocytosis after thrombocytopenic challenge.
  
  
  CONCLUSIONS
  These data suggest that PKCδ is an important megakaryopoietic protein, which regulates signaling induced by thrombopoietin and represents a potential therapeutic target.
authors.affiliation: From the Sol Sherry Thrombosis Research Center (J.C.K., D.B, S.P.K.), Department of Pharmacology and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; and Cardeza Division of Hematology, Department of Medicine, Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, PA (S.E.M.).
authors.forename: John C
authors.initials: JC
authors.lastname: Kostyak
authors.affiliation: From the Sol Sherry Thrombosis Research Center (J.C.K., D.B, S.P.K.), Department of Pharmacology and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; and Cardeza Division of Hematology, Department of Medicine, Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, PA (S.E.M.).
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Bhavanasi
authors.affiliation: From the Sol Sherry Thrombosis Research Center (J.C.K., D.B, S.P.K.), Department of Pharmacology and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; and Cardeza Division of Hematology, Department of Medicine, Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, PA (S.E.M.).
authors.forename: Elisabeta
authors.initials: E
authors.lastname: Liverani
authors.affiliation: From the Sol Sherry Thrombosis Research Center (J.C.K., D.B, S.P.K.), Department of Pharmacology and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; and Cardeza Division of Hematology, Department of Medicine, Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, PA (S.E.M.).
authors.forename: Steven E
authors.initials: SE
authors.lastname: McKenzie
authors.affiliation: From the Sol Sherry Thrombosis Research Center (J.C.K., D.B, S.P.K.), Department of Pharmacology and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; and Cardeza Division of Hematology, Department of Medicine, Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, PA (S.E.M.). spk@temple.edu.
authors.forename: Satya P
authors.initials: SP
authors.lastname: Kunapuli
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000097:blood; D007958:Leukocyte Count; D008533:Megakaryocytes / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010976:Platelet Count; D051745:Protein Kinase C-delta / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013921:Thrombocytopenia / Q000097:blood* / Q000201:enzymology* / Q000276:immunology; D034061:Thrombopoiesis / Q000235:genetics / Q000502:physiology*; D013926:Thrombopoietin / Q000097:blood; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D013926:Thrombopoietin; D051057:Proto-Oncogene Proteins c-akt; D051745:Protein Kinase C-delta; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: blood platelets; megakaryocytes; protein kinase C; thrombopoietin