Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases

Inositol (1,4,5) trisphosphate (Ins(1,4,5)P-3) is a well-known messenger mo lecule that releases calcium from intracellular stores. Homologues with up to six phosphates have been characterized and recently, homologues with sev en or eight phosphate groups, including pyrophosphates, have been identifie d. These homologues are diphosphoinositol pentakisphosphate (PP-InsP(5)/Ins P(7)) and bis(diphospho)inositol tetrakisphosphate (bis-PP-InsP(4)/InsP(8)) [1], the rapid turnover of which [2] is regulated by calcium [2] and adren ergic receptor activity [3]. It has been proposed that the high-energy pyro phosphates might participate in protein phosphorylation [4]. We have purifi ed InsP(6) kinase [5] and PP-InsP(5) kinase [6], both of which display ATP synthase activity, transferring phosphate to ADP, Here, we report the cloni ng of two mammalian InsP(6) kinases and a yeast InsP(6) kinase, Furthermore , we show that the yeast protein, ArgRIII, is an inositol-polyphosphate kin ase that can convert InsP(3) to InsP(4), InsP(5) and InsP(6). We have ident ified a new family of highly conserved inositol-polyphosphate kinases that contain a newly identified, unique consensus sequence.