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Cell Metab. 2011 Feb 2;13(2):215-21. doi: 10.1016/j.cmet.2011.01.007.

Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase.

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  • 1The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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PMID:
21284988
[PubMed - indexed for MEDLINE]
PMCID:
PMC3042716
Free PMC Article
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