Discovery of InsP6-kinases as InsP6 dephosphorylating enzymes provides a new mechanism of cytosolic InsP6 degradation driven by the cellular ATP/ADP ratio

In this study, we demonstrated that lP6Ks change their kinase activity towards InsP6 at decreasing ATP/ADP ratio to an ADP phosphotransferase activity and dephosphorylate InsP6. Enantio-selective analysis revealed that Ins(2,3,4,5,6)P5 is the main InsP5 product of IP6K reaction, whereas the exclusive product of MINPP1 activity is the enantiomer Ins(1,2,4,5,6)P5. While lentiviral RNAi based depletion of MINPP1 at dropping cellular ATP/ADP ratios had no significant impact on Ins(2,3,4,5,6)P5 production, the use of the selective IP6K inhibitor TNP abolished the production of this enatiomer in different types of cells. Furthermore, by analysis of rat tissue and human blood samples all (main and minor) dephosphorylated products of InsP6 were detected in vivo. In summary, we identified IP6Ks as novel nuclear and cytosolic InsP6 (and InsP5) dephosphorylating enzymes whose activity is sensitively driven by a decrease of the cellular ATP/ADP ratio, thus suggesting a role for IP6Ks as cellular adenylate energy ‘sensors’.

Source: BJ Energy - May 28, 2014 Category: Biochemistry Authors: T Wundenberg, N Grabinski, H Lin, G W Mayr Tags: BJ Biomolecules Source Type: research