Wagner P D, Vu N D
Laboratory of Biochemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 2000 Nov 10;275(45):35570-6. doi: 10.1074/jbc.M006106200.
The biochemical mechanism(s) by which Nm23 proteins/nucleoside diphosphate kinases suppress tumor metastasis, inhibit cell motility, and affect cellular differentiation are not known. Here we report that Nm23 proteins can phosphorylate geranyl and farnesyl pyrophosphates to give triphosphates. Wild type Nm23-H1 had higher geranyl and farnesyl pyrophosphate kinase activities than did mutants of Nm23-H1 that do not inhibit cell motility. The phosphorylation of farnesyl pyrophosphate appears to occur in vivo as cells with an elevated level of Nm23-H1 contained more farnesyl triphosphate than did control cells. To our knowledge, this is the first report that farnesyl triphosphate exists in cells. The phosphorylation of farnesyl pyrophosphate by Nm23 proteins could alter isoprenoid metabolism, and cells with an elevated level of Nm23 proteins were found to contain more farnesylated 46- and 24-kDa proteins than did control cells. The phosphorylation of geranyl and farnesyl pyrophosphates by Nm23 proteins provides a novel mechanism by which these proteins might exert their biological effects.
Nm23蛋白/核苷二磷酸激酶抑制肿瘤转移、抑制细胞运动以及影响细胞分化的生化机制尚不清楚。在此我们报告，Nm23蛋白能够将香叶基焦磷酸和法尼基焦磷酸磷酸化生成三磷酸酯。野生型Nm23-H1比不抑制细胞运动的Nm23-H1突变体具有更高的香叶基焦磷酸和法尼基焦磷酸激酶活性。由于Nm23-H1水平升高的细胞比对照细胞含有更多的法尼基三磷酸酯，所以法尼基焦磷酸的磷酸化似乎在体内发生。据我们所知，这是关于细胞中存在法尼基三磷酸酯的首次报道。Nm23蛋白对法尼基焦磷酸的磷酸化可能会改变类异戊二烯代谢，并且发现Nm23蛋白水平升高的细胞比对照细胞含有更多的法尼基化46 kDa和24 kDa蛋白。Nm23蛋白对香叶基焦磷酸和法尼基焦磷酸的磷酸化提供了一种新机制，通过该机制这些蛋白可能发挥其生物学效应。
