Department of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV11LY, UK.
FEBS Lett. 2013 Nov 1;587(21):3464-70. doi: 10.1016/j.febslet.2013.08.035. Epub 2013 Sep 8.
We illuminate the metabolism and the cell-signaling activities of inositol pyrophosphates, by showing that regulation of yeast cyclin-kinase by 1-InsP7 is not conserved for mammalian CDK5, and by kinetically characterizing Ddp1p/DIPP-mediated dephosphorylation of 1-InsP7, 5-InsP7 and InsP8. Each phosphatase exhibited similar Km values for every substrate (range: 35-148 nM). The rank order of kcat values (1-InsP7>5-InsP7=InsP8) was identical for each enzyme, although DIPP1 was 10- to 60-fold more active than DIPP2α/β and DIPP3α/β. We demonstrate InsP8 dephosphorylation preferentially progresses through 1-InsP7. Conversely, we conclude that the more metabolically and functionally significant steady-state route of InsP8 synthesis proceeds via 5-InsP7.
我们通过展示肌醇六磷酸对酵母细胞周期蛋白激酶的调控作用在哺乳动物 CDK5 中并不保守，以及动力学表征 Ddp1p/DIPP 介导的 1-InsP7、5-InsP7 和 InsP8 的去磷酸化，阐明了肌醇焦磷酸的代谢和细胞信号转导活性。每种磷酸酶对每种底物的 Km 值都相似（范围：35-148 nM）。每种酶的 kcat 值（1-InsP7>5-InsP7=InsP8）顺序相同，尽管 DIPP1 的活性比 DIPP2α/β 和 DIPP3α/β 高 10-60 倍。我们证明 InsP8 的去磷酸化优先通过 1-InsP7 进行。相反，我们得出结论，InsP8 合成的更具代谢和功能意义的稳态途径是通过 5-InsP7 进行的。
