Protein Kinase C delta Deficiency Enhances Megakaryopoiesis and Recovery From Thrombocytopenia

作者：Kostyak John C; Bhavanasi Dheeraj; Liverani Elisabeta; McKenzie Steven E; Kunapuli Satya P^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2014, 34(12): 2579-U253.

DOI：10.1161/ATVBAHA.114.304492

• blood platelets
• megakaryocytes
• protein kinase C
• thrombopoietin

Objective-We previously determined that protein kinase C delta (PKCd) regulates platelet function. However, the function of PKCd in megakaryopoiesis is unknown. %26lt;br%26gt;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%26lt;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%26lt;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. %26lt;br%26gt;Conclusions-These data suggest that PKC delta is an important megakaryopoietic protein, which regulates signaling induced by thrombopoietin and represents a potential therapeutic target.

• 出版日期2014-12