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Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase.

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.

Pubmed ID: 21284988

Authors

  • Kim S
  • Kim SF
  • Maag D
  • Maxwell MJ
  • Resnick AC
  • Juluri KR
  • Chakraborty A
  • Koldobskiy MA
  • Cha SH
  • Barrow R
  • Snowman AM
  • Snyder SH

Journal

Cell metabolism

Publication Data

February 2, 2011

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA-00074
  • Agency: NIDA NIH HHS, Id: DA-00266
  • Agency: NIDA NIH HHS, Id: K05 DA000074
  • Agency: NIDA NIH HHS, Id: K05 DA000074-30
  • Agency: NCI NIH HHS, Id: K99 CA134914
  • Agency: NCI NIH HHS, Id: K99 CA134914-01
  • Agency: NIDA NIH HHS, Id: P50 DA000266
  • Agency: NIDA NIH HHS, Id: P50 DA000266-40
  • Agency: NCI NIH HHS, Id: R00 CA134914
  • Agency: NCI NIH HHS, Id: R00 CA134914-02
  • Agency: NCI NIH HHS, Id: R00 CA134914-03
  • Agency: NIDDK NIH HHS, Id: R01 DK084336
  • Agency: NIDDK NIH HHS, Id: R01 DK084336-01A1
  • Agency: NIDDK NIH HHS, Id: R01DK084336

Mesh Terms

  • Amino Acid Substitution
  • Amino Acids
  • Animals
  • Biocatalysis
  • Cell Line
  • Fibroblasts
  • Humans
  • Mice
  • Mutation
  • Phosphotransferases (Alcohol Group Acceptor)
  • Protein Binding
  • Signal Transduction
  • TOR Serine-Threonine Kinases