TY - JOUR
T1 - Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases
AU - Saiardi, Adolfo
AU - Erdjument-Bromage, Hediye
AU - Snowman, Adele M.
AU - Tempst, Paul
AU - Snyder, Solomon H.
N1 - Funding Information:
We are grateful to A. Riccio for reading the manuscript and for helpful comments. We are indebted to Lynne Lacomis and Anita Grewal for help with mass spectrometric analysis. This work was supported by NCI core grant P30 CA08748 (P.T.), MH18501 (S.H.S.) and Research Scientist Award DA00074 (S.H.S.).
PY - 1999/11/18
Y1 - 1999/11/18
N2 - Inositol (1,4,5) trisphosphate (Ins(1,4,5)P3) is a well-known messenger molecule that releases calcium from intracellular stores. Homologues with up to six phosphates have been characterized and recently, homologues with seven or eight phosphate groups, including pyrophosphates, have been identified. These homologues are diphosphoinositol pentakisphosphate (PP-InsP5/InsP7) and bis(diphospho)inositol tetrakisphosphate (bis-PP-InsP4/InsP8) [1], the rapid turnover of which [2] is regulated by calcium [2] and adrenergic receptor activity [3]. It has been proposed that the high-energy pyrophosphates might participate in protein phosphorylation [4]. We have purified InsP6 kinase [5] and PP-InsP5 kinase [6], both of which display ATP synthase activity, transferring phosphate to ADP. Here, we report the cloning of two mammalian InsP6 kinases and a yeast InsP6 kinase. Furthermore, we show that the yeast protein, ArgRIII, is an inositol-polyphosphate kinase that can convert InsP3 to InsP4, InsP5 and insP6. We have identified a new family of highly conserved inositol-polyphosphate kinases that contain a newly identified, unique consensus sequence.
AB - Inositol (1,4,5) trisphosphate (Ins(1,4,5)P3) is a well-known messenger molecule that releases calcium from intracellular stores. Homologues with up to six phosphates have been characterized and recently, homologues with seven or eight phosphate groups, including pyrophosphates, have been identified. These homologues are diphosphoinositol pentakisphosphate (PP-InsP5/InsP7) and bis(diphospho)inositol tetrakisphosphate (bis-PP-InsP4/InsP8) [1], the rapid turnover of which [2] is regulated by calcium [2] and adrenergic receptor activity [3]. It has been proposed that the high-energy pyrophosphates might participate in protein phosphorylation [4]. We have purified InsP6 kinase [5] and PP-InsP5 kinase [6], both of which display ATP synthase activity, transferring phosphate to ADP. Here, we report the cloning of two mammalian InsP6 kinases and a yeast InsP6 kinase. Furthermore, we show that the yeast protein, ArgRIII, is an inositol-polyphosphate kinase that can convert InsP3 to InsP4, InsP5 and insP6. We have identified a new family of highly conserved inositol-polyphosphate kinases that contain a newly identified, unique consensus sequence.
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U2 - 10.1016/S0960-9822(00)80055-X
DO - 10.1016/S0960-9822(00)80055-X
M3 - Article
C2 - 10574768
AN - SCOPUS:0033581832
SN - 0960-9822
VL - 9
SP - 1323
EP - 1326
JO - Current Biology
JF - Current Biology
IS - 22
ER -