John C Kostyak1, Dheeraj Bhavanasi1, Elisabeta Liverani1, Steven E McKenzie1, Satya P Kunapuli2. 1. 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.). 2. 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.
Abstract
OBJECTIVE: We previously determined that protein kinase C δ (PKCδ) regulates platelet function. However, the function of PKCδ in megakaryopoiesis is unknown. APPROACH AND 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.
OBJECTIVE: We previously determined that protein kinase C δ (PKCδ) regulates platelet function. However, the function of PKCδ in megakaryopoiesis is unknown. APPROACH AND 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: S Oshevski; M C Le Bousse-Kerdilès; D Clay; Z Levashova; N Debili; N Vitral; C Jasmin; M Castagna Journal: Biochem Biophys Res Commun Date: 1999-10-05 Impact factor: 3.575
Authors: T Kato; K Ogami; Y Shimada; A Iwamatsu; Y Sohma; H Akahori; K Horie; A Kokubo; Y Kudo; E Maeda Journal: J Biochem Date: 1995-07 Impact factor: 3.387