ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis

Ali ES, Sahu U, Villa E, O'Hara BP, Gao P, Beaudet C, Wood AW, Asara JM, Ben-Sahra I · 2020 · Molecular Cell · Atlas ID ALI2020

What this study shows

The Atlas records several routes by which mTORC1 drives purine synthesis. This study shows mTORC1 is not the only growth pathway with that power: RAS-ERK signalling stimulates purine synthesis directly and within minutes, because ERK2 - but not ERK1 - phosphorylates the purine synthesis enzyme PFAS at Thr619. Cells expressing a PFAS that cannot be phosphorylated make fewer purines, form fewer colonies and grow smaller tumors. Two points bound the mTOR claim: the control is posttranslational, so it acts far faster than transcription or translation, and it is a parallel input, so purine synthesis in a RAS-driven tumor is not read out from mTORC1 activity alone.

Abstract

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The RAS-ERK/MAPK (RAS-extracellular signal-regulated kinase/mitogen-activated protein kinase) pathway integrates growth-promoting signals to stimulate cell growth and proliferation, at least in part, through alterations in metabolic gene expression. However, examples of direct and rapid regulation of the metabolic pathways by the RAS-ERK pathway remain elusive.

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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 cancer cells; tumor) 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 cancer cells; tumor
Journal	Molecular Cell
Year	2020
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1016/j.molcel.2020.05.001 · PMID 32485148 · Free full text (PMC7306006)

Extracted findings

Intervention	Genetic (PFAS T619A); ERK pathway activation
Target	RAS / ERK2 / PFAS (de novo purine synthesis)
Model	Human cancer cells; mouse tumors
Effect	ERK2 phosphorylates PFAS at T619 to stimulate de novo purine synthesis, supporting cell proliferation and tumor growth

Cite this paper

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Ali, E. S., Sahu, U., Villa, E., O'Hara, B. P., Gao, P., Beaudet, C., Wood, A. W., Asara, J. M., & Ben-Sahra, I. (2020). ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis. Molecular Cell. https://doi.org/10.1016/j.molcel.2020.05.001

@article{ALI2020,
  author       = {Ali, E. S. and Sahu, U. and Villa, E. and O'Hara, B. P. and Gao, P. and Beaudet, C. and Wood, A. W. and Asara, J. M. and Ben-Sahra, I.},
  title        = {{ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis}},
  journal      = {Molecular Cell},
  year         = {2020},
  doi          = {10.1016/j.molcel.2020.05.001},
  note         = {PMID: 32485148},
}

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 ALI2020) [Data set]. https://mtor-atlas.org/study/ALI2020/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ALI2020,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ALI2020},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ALI2020/},
  doi          = {10.5281/zenodo.22059963}
}