Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P-41-kinase/Ins(1,3,4)P-3 5/6-kinase

We describe a human cDNA encoding 1-kinase activity that inactivates Ins(3, 4,5,6)P-4, an inhibitor of chloride-channel conductance that regulates epit helial salt and fluid secretion, as well as membrane excitability. Unexpect edly, we further discovered that this enzyme has alternative positional spe cificity (5/6-kinase activity) towards a different substrate, namely Ins(1, 3,3)P-3. Kinetic data from a recombinant enzyme indicate that Ins(1,3,4)P-3 (K-m = 0.3 muM; V-max = 320 pmol/min per mug) and Ins(3,4,5,6)P-4 (K-m = 0 .1 muM; V-max = 780 pmol/min per mug) actively compete for phosphorylation in vivo. This competition empowers the kinase with multitasking capability in several key aspects of inositol phosphate signalling.