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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

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

Kostyak John C JC   Bhavanasi Dheeraj D   Liverani Elisabeta E   McKenzie Steven E SE   Kunapuli Satya P SP  

Arteriosclerosis, thrombosis, and vascular biology 20141030 12

<h4>Objective</h4>We previously determined that protein kinase C δ (PKCδ) regulates platelet function. However, the function of PKCδ in megakaryopoiesis is unknown.<h4>Approach and results</h4>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 aft  ...[more]

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