Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34

Gulati P, Gaspers LD, Dann SG, Joaquin M, Nobukuni T, Natt F, Kozma SC, Thomas AP, Thomas G · 2008 · Cell Metabolism · Atlas ID GUL2008

What this study shows

In cultured human cells, adding amino acids raised the free calcium level inside the cell, and this rise was needed for amino acids to switch on mTORC1 and the lipid kinase hVps34. Calcium-bound calmodulin bound directly to a conserved motif in hVps34, and the authors showed this motif was needed for hVps34 lipid kinase activity and for the increase in mTORC1 signalling. The paper proposed a route from amino acids to mTORC1 that runs through class III PI3K (hVps34) rather than the class I PI3K used by insulin and growth factors. Boundary: Human cell lines only. The calcium/hVps34 route was proposed before the Rag-Ragulator-GATOR model and is not part of the current consensus amino-acid pathway. Drafted from the abstract only.

Abstract

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Excess levels of circulating amino acids (AAs) play a causal role in specific human pathologies, including obesity and type 2 diabetes. Moreover, obesity and diabetes are contributing factors in the development of cancer, with recent studies suggesting that this link is mediated in part by AA activation of mammalian target of rapamycin (mTOR) Complex 1. AAs appear to mediate this response through class III phosphatidylinositol 3-kinase (PI3K), or human vacuolar protein sorting 34 (hVps34), rather than through the canonical class I PI3K pathway used by growth factors and hormones.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cell lines (HEK293 and HeLa per MeSH); intracellular Ca2+ imaging; hVps34 site-directed mutants; S6K1 phosphorylation readouts) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human cell lines (HEK293 and HeLa per MeSH); intracellular Ca2+ imaging; hVps34 site-directed mutants; S6K1 phosphorylation readouts
Journal	Cell Metabolism
Year	2008
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.cmet.2008.03.002 · PMID 18460336 · Free full text (PMC2587347)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Amino acid stimulation; Ca2+ chelation; hVps34 CaM-binding motif mutants
Target	hVps34 lipid kinase activity; mTORC1 signalling
Model	Human cell lines
Effect	Amino acids -> rise in intracellular Ca2+ -> Ca2+/CaM binds hVps34 -> increased mTORC1 signalling

In the Atlas

Cite this paper

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Gulati, P., Gaspers, L. D., Dann, S. G., Joaquin, M., Nobukuni, T., Natt, F., Kozma, S. C., Thomas, A. P., & Thomas, G. (2008). Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34. Cell Metabolism. https://doi.org/10.1016/j.cmet.2008.03.002

@article{GUL2008,
  author       = {Gulati, P. and Gaspers, L. D. and Dann, S. G. and Joaquin, M. and Nobukuni, T. and Natt, F. and Kozma, S. C. and Thomas, A. P. and Thomas, G.},
  title        = {{Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34}},
  journal      = {Cell Metabolism},
  year         = {2008},
  doi          = {10.1016/j.cmet.2008.03.002},
  note         = {PMID: 18460336},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record GUL2008) [Data set]. https://mtor-atlas.org/study/GUL2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GUL2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GUL2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GUL2008/},
  doi          = {10.5281/zenodo.22059963}
}

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