期刊
BIOCHEMICAL JOURNAL
卷 450, 期 -, 页码 115-125出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20121524
关键词
endocytosis; Ins(1,2,3,4,5,6)P-6 (InsP(6)); micro nutrients; myo-inositol; phytase; phytate; tumour cell proliferation
InsP(6) [Ins(1,2,3,4,5,6)P-6; phytate] is the most abundant inositol phosphate in mammalian cells with cytosolic/nuclear concentrations of up to 50 mu M. We noticed that InsP(6) in culture medium at a concentration of <= 50 mu M significantly stimulates H1299 tumour cell growth, whereas larger concentrations of InsP(6) inhibit growth. A detailed study of the fate of 30 mu M InsP(6) added to H199 cells revealed a major fraction of InsP(6) initially precipitates as cell-surface metal complexes, but becomes slowly re-solubilized by extracellular dephosphorylation first to InsP(3) isomers and subsequently to free myo-inositol. The precipitated metal InsP(6) complex is endocytosed in a receptor-independent but intact-glycocalyx-dependent manner and appears in lysosomes, where it is immediately dephosphorylated to Ins(1,2,4,5,6)P-5 and very slowly to free inositol. By RNA knockdown, we identified secreted and lysosome targeted MINPP1 (multiple inositol-polyphosphate phosphatase 1), the mammalian 3-phytase, to be essentially involved both in extracellular and in lysosomal InsP(6) dephosphorylation. The results of the present study indicate that tumour cells employ this enzyme to utilize the micronutrients myo-inositol and metal-phosphate when encountering extracellular InsP(6) and thus to enhance their growth potential.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据