Amino Acid Signaling to MTOR Mediated by Inositol Polyphosphate Multikinase
Open accessAbstract
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.
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IPMK has roles in nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation.
“Initially identified in yeast and later recognized as essential for mammalian embryonic development, IPMK has transitioned from a niche interest to a focal point in studies of nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [23]
The Introduction and Results report IPMK’s role in amino-acid signaling to mTOR and its involvement in insulin-stimulated mTORC2 signaling. The Introduction identifies IPMK in yeast, and the Discussion reports that IPMK knockout mice die early in development. Our copy does not establish a role for IPMK in mRNA transport or transcription regulation; transcription appears only in cited reference titles. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIPMK functions in mRNA export, chromatin remodeling, transcription, nutrient sensing, and growth factor signaling.
“Its diverse functions span a wide range of cellular processes, including mRNA export [17,18], chromatin remodeling [19,20], transcription [21,22], nutrient sensing [23], and growth factor signaling [15].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [23]
IPMK stabilizes the mTORC1 complex and facilitates amino acid sensing in cells.
“Kim et al. [23] were the first to demonstrate that IPMK stabilizes the mTORC1 complex and facilitates amino acid sensing in cells.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [23]
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Cites
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“Kim et al. [23] were the first to demonstrate that IPMK stabilizes the mTORC1 complex and facilitates amino acid sensing in cells.”
Influential
- Authors
- Kim, S., Kim, S. F., Maag, D., Maxwell, M. J., Resnick, A. C., Juluri, K. R., Chakraborty, A., Koldobskiy, M. A., Cha, S. H., Barrow, R., Snowman, A. M., & Snyder, S. H.
- Affiliations
- Johns Hopkins University (US)
- University of Pennsylvania (US)
- Corresponding author
- Snyder, Solomon H.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 13
- Issue
- 2
- Pages
- 215-221
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3042716
- OpenAlex
- W2162895146
- Cited by
- 144
- References
- 8
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 11 · 2016: 12 · 2015: 11 · 2014: 11 · 2013: 17 · 2012: 11
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (P50DA000266, DA 00074, DA.00266, K05DA000074)
- National Cancer Institute (R00CA134914, K99CA134914)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK084336)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- inositol polyphosphate multikinase, mTORC1, amino acid signaling, raptors, protein synthesis regulation, protein-protein interaction, obesity, diabetes mellitus
- MeSH terms
- Amino Acids, Animals, Cell Line, Fibroblasts, Humans, Mutation, Protein Binding, Signal Transduction, Phosphotransferases (Alcohol Group Acceptor), Amino Acid Substitution, Mice, Biocatalysis, TOR Serine-Threonine Kinases
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