Protein kinase C ? deficiency enhances megakaryopoiesis and recovery from thrombocytopenia.

ABSTRACT: We previously determined that protein kinase C ? (PKC?) regulates platelet function. However, the function of PKC? in megakaryopoiesis is unknown.Using PKC?(-/-) and wild-type littermate mice, we found that deficiency of PKC? 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 PKC?(-/-) mouse bone marrow after culturing with exogenous thrombopoietin compared with wild-type (P<0.05). Importantly, thrombopoietin-induced signaling was also altered with PKC? deletion because both extracellular signal-regulated kinase and Akt308 phosphorylation were heightened in PKC?(-/-) megakaryocytes compared with wild-type. Finally, PKC?(-/-) mice recovered faster and had a heightened rebound thrombocytosis after thrombocytopenic challenge.These data suggest that PKC? is an important megakaryopoietic protein, which regulates signaling induced by thrombopoietin and represents a potential therapeutic target.

SUBMITTER: Kostyak JC 

PROVIDER: S-EPMC4239172 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature