American Heart Association, Arteriosclerosis, Thrombosis, and Vascular Biology, 12(34), p. 2579-2585, 2014
DOI: 10.1161/atvbaha.114.304492
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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.