Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, Bilbao, Spain.
FEBS Lett. 2010 Feb 5;584(3):517-24. doi: 10.1016/j.febslet.2009.11.086. Epub 2009 Nov 27.
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.
我们之前的研究表明，神经酰胺-1-磷酸（C1P）可刺激成纤维细胞和巨噬细胞增殖，但该作用的具体机制尚未完全阐明。本文研究发现，C1P 可诱导骨髓来源的巨噬细胞中蛋白激酶 C-α（PKC-α）从可溶性部分向膜部分转位。该酶的转位伴随着丝氨酸 657 残基的磷酸化。PKC-α 的激活不依赖于先前刺激的磷脂酰肌醇依赖性或磷脂酰胆碱依赖性磷酯酶 C 活性，但需要激活鞘磷脂的合成。抑制 PKC-α 的激活也可阻断 C1P 刺激的巨噬细胞增殖，表明该酶对于 C1P 的有丝分裂效应是必需的。
