Activation of protein kinase C-α is essential for stimulation of cell proliferation by ceramide 1-phosphate

被引:47
作者
Gangoiti, Patricia [1 ]
Granado, Maria H. [1 ]
Arana, Lide [1 ]
Ouro, Alberto [1 ]
Gomez-Munoz, Antonio [1 ]
机构
[1] Univ Basque Country, Fac Sci & Technol, Dept Biochem & Mol Biol, Bilbao 48080, Spain
来源
FEBS LETTERS | 2010年 / 584卷 / 03期
关键词
Ceramide; 1-phosphate; Cell proliferation; Macrophage; Phosphoinositide-3-kinase; Protein kinase C; Sphingolipid; SPHINGOSINE; 1-PHOSPHATE; SPHINGOMYELIN SYNTHASE; ACID SPHINGOMYELINASE; MACROPHAGE SURVIVAL; BLOCKS APOPTOSIS; DNA-SYNTHESIS; B PATHWAY; CERAMIDE-1-PHOSPHATE; INVOLVEMENT; PHAGOCYTOSIS;
D O I
10.1016/j.febslet.2009.11.086
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:517 / 524
页数:8
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