Protein Kinase C δ Deficiency Enhances Megakaryopoiesis and Recovery From Thrombocytopenia

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