Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis

Ruvinsky I, Sharon N, Lerer T, Cohen H, Stolovich-Rain M, Nir T, Dor Y, Zisman P, Meyuhas O · 2005 · Genes & Development · Atlas ID RUV2005

What this study shows

The authors made knock-in mice in which all five phosphorylatable serines of ribosomal protein S6 were replaced by alanine, so rpS6 could not be phosphorylated. Contrary to the then widely accepted model, translational control of 5'TOP mRNAs was unaffected. Fibroblasts from these mice made protein faster and divided faster, yet were smaller than wild-type cells, and rapamycin did not shrink them further, which points to rpS6 phosphorylation as a downstream effector of mTOR in cell-size control. Adult mutant mice also had smaller pancreatic beta-cells, less pancreatic insulin, low blood insulin and impaired glucose tolerance. Boundary: Mouse knock-in and mouse cells. Separates rpS6 phosphorylation from 5'TOP control in these systems; not tested in people. Drafted from the abstract only.

Abstract

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The regulated phosphorylation of ribosomal protein (rp) S6 has attracted much attention since its discovery in 1974, yet its physiological role has remained obscure. To directly address this issue, we have established viable and fertile knock-in mice, whose rpS6 contains alanine substitutions at all five phosphorylatable serine residues (rpS6(P-/-)). Here we show that contrary to the widely accepted model, this mutation does not affect the translational control of TOP mRNAs.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Knock-in mice with all five rpS6 phosphorylation sites mutated to alanine (rpS6P-/-); embryonic fibroblasts; pancreatic beta-cells; glucose tolerance tests); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Knock-in mice with all five rpS6 phosphorylation sites mutated to alanine (rpS6P-/-); embryonic fibroblasts; pancreatic beta-cells; glucose tolerance tests
Journal	Genes & Development
Year	2005
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1101/gad.351605 · PMID 16166381 · Free full text (PMC1221890)

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	Knock-in of non-phosphorylatable rpS6 (five Ser->Ala)
Target	5'TOP translation; protein synthesis; cell size; beta-cell size; glucose tolerance
Model	Mouse
Effect	Loss of rpS6 phosphorylation reduces cell and beta-cell size and impairs glucose tolerance without affecting 5'TOP translation

In the Atlas

Cite this paper

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Ruvinsky, I., Sharon, N., Lerer, T., Cohen, H., Stolovich-Rain, M., Nir, T., Dor, Y., Zisman, P., & Meyuhas, O. (2005). Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis. Genes & Development. https://doi.org/10.1101/gad.351605

@article{RUV2005,
  author       = {Ruvinsky, I. and Sharon, N. and Lerer, T. and Cohen, H. and Stolovich-Rain, M. and Nir, T. and Dor, Y. and Zisman, P. and Meyuhas, O.},
  title        = {{Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis}},
  journal      = {Genes & Development},
  year         = {2005},
  doi          = {10.1101/gad.351605},
  note         = {PMID: 16166381},
}

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 RUV2005) [Data set]. https://mtor-atlas.org/study/RUV2005/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_RUV2005,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record RUV2005},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/RUV2005/},
  doi          = {10.5281/zenodo.22059963}
}

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