title: Arginine transcriptional response does not require inositol phosphate synthesis.
abstract: Inositol phosphates are key signaling molecules affecting a large variety of cellular processes. Inositol-polyphosphate multikinase (IPMK) is a central component of the inositol phosphate biosynthetic routes, playing essential roles during development. IPMK phosphorylates inositol 1,4,5-trisphosphate to inositol tetrakisphosphate and subsequently to inositol pentakisphosphate and has also been described to function as a lipid kinase. Recently, a catalytically inactive mammalian IPMK was reported to be involved in nutrient signaling by way of mammalian target of rapamycin and AMP-activated protein kinase. In yeast, the IPMK homologue, Arg82, is the sole inositol-trisphosphate kinase. Arg82 has been extensively studied as part of the transcriptional complex regulating nitrogen sensing, in particular arginine metabolism. Whether this role requires Arg82 catalytic activity has long been a matter of contention. In this study, we developed a novel method for the real time study of promoter strength in vivo and used it to demonstrate that catalytically inactive Arg82 fully restored the arginine-dependent transcriptional response. We also showed that expression in yeast of catalytically active, but structurally very different, mammalian or plant IPMK homologue failed to restore arginine regulation. Our work indicates that inositol phosphates do not regulate arginine-dependent gene expression.
authors.affiliation: Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bosch
authors.forename: Adolfo
authors.initials: A
authors.lastname: Saiardi
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D055162:Biocatalysis; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009952:Ornithine / Q000378:metabolism / Q000494:pharmacology; D009954:Ornithine Carbamoyltransferase / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D017851:Phosphotransferases (Carboxyl Group Acceptor) / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D000644:Quaternary Ammonium Compounds / Q000378:metabolism / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C492864:Arg5,6 protein, S cerevisiae; D007295:Inositol Phosphates; D009097:Multienzyme Complexes; D000644:Quaternary Ammonium Compounds; D029701:Saccharomyces cerevisiae Proteins; D015544:Inositol 1,4,5-Trisphosphate; D001120:Arginine; D009952:Ornithine; D000445:Aldehyde Oxidoreductases; D009954:Ornithine Carbamoyltransferase; C451259:arg3 protein, S cerevisiae; C425775:ARG82 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase; D017851:Phosphotransferases (Carboxyl Group Acceptor)