Activation of protein kinase C-α is essential for stimulation of cell proliferation by ceramide 1-phosphate
Activation of protein kinase C-α is essential for stimulation of cell proliferation by ceramide 1-phosphate
复制标题
DOI：
10.1016/j.febslet.2009.11.086
复制
发表时间：
2010-02-05
期刊：
影响因子：
3.5
通讯作者：
Gomez-Munoz, Antonio
中科院分区：
文献类型：
--
作者：
Gangoiti, Patricia;Granado, Maria H.;Gomez-Munoz, Antonio
我们以前证明了神经酰胺-1-磷酸(C1P)刺激成纤维细胞和巨噬细胞增殖，但参与这一作用的机制只有部分描述。在这里，我们证明了C1P诱导蛋白激酶C-α(PKC-α)从骨髓来源的巨噬细胞的可溶性部分移位到膜部分。该酶的易位伴随着其在Ser657残基上的磷酸化。PKC-α的激活不依赖于先前对磷脂酰肌醇依赖或磷脂酰胆碱依赖的磷脂酶C活性的刺激，但需要激活鞘磷脂的合成。抑制PKC-α的激活也阻断了C1P刺激的巨噬细胞增殖，表明该酶对C1P的有丝分裂作用是必不可少的。(C)2009年欧洲生化学会联合会。爱思唯尔出版，版权所有。
We previously demonstrated that ceramide-1-phosphate (C1P) stimulates fibroblast and macrophage proliferation, but the mechanisms involved in this action have only been partially described. Here we demonstrate that C1P induces translocation of protein kinase C-alpha (PKC-alpha) from the soluble to the membrane fraction of bone marrow-derived macrophages. Translocation of this enzyme was accompanied by its phosphorylation on Ser 657 residue. Activation of PKC-alpha was independent of prior stimulation of phosphatidylinositol-dependent or phosphatidylcholine-dependent phospholipase C activities, but required activation of sphingomyelin synthesis. Inhibition of PKC-alpha activation also blocked C1P-stimulated macrophage proliferation indicating that this enzyme is essential for the mitogenic effect of C1P. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.