Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase

Nobukuni T, Joaquin M, Roccio M, Dann SG, Kim SY, Gulati P, Byfield MP, Backer JM, Natt F, Bos JL, Zwartkruis FJ, Thomas G · 2005 · Proc Natl Acad Sci U S A · Atlas ID NOB2005

What this study shows

The companion paper to BYF2005, from a different laboratory: the amino acid input to mTORC1 is separate from the insulin input and runs through class 3 PI3K (hVps34), not through class 1 PI3K. Historically important because it states that the amino acid branch is the older one and that insulin signalling was grafted onto it. Boundary: cell lines, pharmacological and knockdown evidence; the later Rag/Ragulator account describes a different route to the same target and the two have never been fully reconciled.

Abstract

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During the evolution of metazoans and the rise of systemic hormonal regulation, the insulin-controlled class 1 phosphatidylinositol 3OH-kinase (PI3K) pathway was merged with the primordial amino acid-driven mammalian target of rapamycin (mTOR) pathway to control the growth and development of the organism. Insulin regulates mTOR function through a recently described canonical signaling pathway, which is initiated by the activation of class 1 PI3K. However, how the amino acid input is integrated with that of the insulin signaling pathway is unclear.

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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) 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
Journal	Proc Natl Acad Sci U S A
Year	2005
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1073/pnas.0506925102 · PMID 16176982

Cite this paper

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Nobukuni, T., Joaquin, M., Roccio, M., Dann, S. G., Kim, S. Y., Gulati, P., Byfield, M. P., Backer, J. M., Natt, F., Bos, J. L., Zwartkruis, F. J., & Thomas, G. (2005). Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.0506925102

@article{NOB2005,
  author       = {Nobukuni, T. and Joaquin, M. and Roccio, M. and Dann, S. G. and Kim, S. Y. and Gulati, P. and Byfield, M. P. and Backer, J. M. and Natt, F. and Bos, J. L. and Zwartkruis, F. J. and Thomas, G.},
  title        = {{Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase}},
  journal      = {Proc Natl Acad Sci U S A},
  year         = {2005},
  doi          = {10.1073/pnas.0506925102},
  note         = {PMID: 16176982},
}

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 NOB2005) [Data set]. https://mtor-atlas.org/study/NOB2005/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_NOB2005,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record NOB2005},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/NOB2005/},
  doi          = {10.5281/zenodo.22059963}
}