mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycin

Kang SA, Pacold ME, Cervantes CL, Lim D, Lou HJ, Ottina K, Gray NS, Turk BE, Yaffe MB, Sabatini DM · 2013 · Science · Atlas ID KAN2013

What this study shows

Each mTORC1 phosphorylation site has its own intrinsic 'substrate quality'. Good substrates stay phosphorylated when mTORC1 is partly inhibited by rapamycin or starvation, poor ones drop out first, and changing a few residues around a site shifts its sensitivity in cells. One level of mTORC1 activity can therefore produce different output profiles.

Abstract

ShowHide

The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) protein kinase promotes growth and is the target of rapamycin, a clinically useful drug that also prolongs life span in model organisms. A persistent mystery is why the phosphorylation of many bona fide mTORC1 substrates is resistant to rapamycin. We find that the in vitro kinase activity of mTORC1 toward peptides encompassing established phosphorylation sites varies widely and correlates strongly with the resistance of the sites to rapamycin, as well as to nutrient and growth factor starvation within cells.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human and mouse cell lines; in vitro mTORC1 kinase assays on peptide substrates) 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 and mouse cell lines; in vitro mTORC1 kinase assays on peptide substrates
Journal	Science
Year	2013
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.1236566 · PMID 23888043 · Free full text (PMC3771538)

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	Rapamycin; Torin1; amino-acid and growth-factor starvation; point mutations around phosphorylation sites
Target	mTORC1 substrate sites (S6K1, 4E-BP1, ULK1 and others)
Model	Human and mouse cell lines; in vitro
Effect	Site-intrinsic substrate quality predicts which mTORC1 outputs are rapamycin- and starvation-resistant

In the Atlas

Links in the pathway map

Open questions that cite this study

Cited as supporting evidence for the open question A sensor/autophagy biomarker panel as a surrogate endpoint for human trials.

Cite this paper

ShowHide

Kang, S. A., Pacold, M. E., Cervantes, C. L., Lim, D., Lou, H. J., Ottina, K., Gray, N. S., Turk, B. E., Yaffe, M. B., & Sabatini, D. M. (2013). mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycin. Science. https://doi.org/10.1126/science.1236566

@article{KAN2013,
  author       = {Kang, S. A. and Pacold, M. E. and Cervantes, C. L. and Lim, D. and Lou, H. J. and Ottina, K. and Gray, N. S. and Turk, B. E. and Yaffe, M. B. and Sabatini, D. M.},
  title        = {{mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycin}},
  journal      = {Science},
  year         = {2013},
  doi          = {10.1126/science.1236566},
  note         = {PMID: 23888043},
}

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 KAN2013) [Data set]. https://mtor-atlas.org/study/KAN2013/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_KAN2013,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record KAN2013},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/KAN2013/},
  doi          = {10.5281/zenodo.22059963}
}

Was this page useful?