title: Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase.
abstract: mTOR complex 1 (mTORC1; mammalian target of rapamycin [mTOR] in complex with raptor) is a key regulator of protein synthesis and cell growth in response to nutrient amino acids. Here we report that inositol polyphosphate multikinase (IPMK), which possesses both inositol phosphate kinase and lipid kinase activities, regulates amino acid signaling to mTORC1. This regulation is independent of IPMK's catalytic function, instead reflecting its binding with mTOR and raptor, which maintains the mTOR-raptor association. Thus, IPMK appears to be a physiologic mTOR cofactor, serving as a determinant of mTORC1 stability and amino acid-induced mTOR signaling. Substances that block IPMK-mTORC1 binding may afford therapeutic benefit in nutrient amino acid-regulated conditions such as obesity and diabetes.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Seyun
authors.initials: S
authors.lastname: Kim
authors.forename: Sangwon F
authors.initials: SF
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Maag
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Maxwell
authors.forename: Adam C
authors.initials: AC
authors.lastname: Resnick
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Juluri
authors.forename: Anutosh
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Michael A
authors.initials: MA
authors.lastname: Koldobskiy
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Cha
authors.forename: Roxanne
authors.initials: R
authors.lastname: Barrow
authors.forename: Adele M
authors.initials: AM
authors.lastname: Snowman
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D055162:Biocatalysis; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases