ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis
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.
Read the full abstract on PubMed →At a glance
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| 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 | 2026-10-01 |
| Source | DOI 10.1016/j.molcel.2020.05.001 · PMID 32485148 · Free full text (PMC7306006) |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
Pathway relations
Supports
ERK / RSK (MAPK) activates Nucleotide synthesisStrongest evidence: M (Molecular — cells, biochemistry, structure) · emerging, few independent studies · Status: Proposed
plausible in people, not shown directly
Human cancer cell lines and xenograft tumours; ERK2, not ERK1; post-translational and parallel to mTORC1. Single study.
People in the Atlas
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Showed as a Ben-Sahra-lab postdoc that ERK2 directly activates the purine-synthesis enzyme PFAS, and that mTORC1 increases bicarbonate import through SLC4A7 to fuel nucleotide synthesis. His Kentucky lab studies how growth signals control nucleotide metabolism in cancer
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Showed as a postdoc in Brendan Manning's lab that mTORC1 drives both pyrimidine and purine synthesis, through two different mechanisms. His Northwestern lab has extended this to bicarbonate import, SAM synthesis and ERK control of purine production
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Showed that the building blocks of RNA also tell mitochondria how fast to burn fuel
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First author of the study showing that mTORC1 raises production of the methyl donor SAM through MAT2A and boosts m6A mRNA methylation to support protein synthesis and cell growth.
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As lab manager of Issam Ben-Sahra's lab at Northwestern, contributed to its studies of how mTORC1 and ERK control nucleotide synthesis, SAM production and bicarbonate import
More: 4 other authors
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Directs the Northwestern metabolomics core that supplied mass-spectrometry metabolite measurements for three Ben-Sahra lab studies on how mTORC1 and ERK signalling drive nucleotide and SAM synthesis.
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Mass-spectrometry specialist whose core facility supplied metabolomics and proteomics for several mTOR studies, including measurements of purine, pyrimidine and SAM metabolism downstream of mTORC1.
No profile yet: Beaudet C, Wood AW
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More related studies
- M mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle
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- M Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1
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Topics
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 | 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 |
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