"Trojan" Methionine Probe Reveals PKM2 as a Methionine-Sensing Protein in the mTORC1 Pathway

Sang Z, Zheng Y, Wang X, Wu C, Zhao J, Wang JJ, Sui S, Wang J · 2026 · Journal of the American Chemical Society · Atlas ID SANG2026

What this study shows

Identifies PKM2 as a direct methionine sensor for mTORC1. A photoaffinity methionine analogue plus chemoproteomics showed that PKM2 binds free methionine through a distinct recognition pocket — independently of its glycolytic enzyme activity — and transduces methionine availability to mTORC1 via the GATOR2 complex. Complements SAMTOR (GU2017), which reads the methionine metabolite SAM rather than methionine itself, and suggests a route to a pharmacological "methionine pseudostarvation" state.

Abstract

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Methionine (Met) plays a pivotal role in numerous cellular functions. Methionine restriction has been demonstrated to provide metabolic benefits in aging, obesity, diabetes and as an adjunct to cancer therapy. However, the methionine-sensing proteins and how cells directly sense the methionine level have remained elusive. In this study, we developed a photoaffinity analogue of methionine to capture proteins that specifically recognize and sense methionine in living 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 cells (chemoproteomics / photoaffinity probe)) 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 cells (chemoproteomics / photoaffinity probe)
Journal	Journal of the American Chemical Society
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1021/jacs.6c06772 · PMID 42677553

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	Photoaffinity methionine analogue (chemoproteomic capture); methionine restriction/repletion
Target	PKM2 / GATOR2 / mTORC1 (methionine sensing)
Model	Human cells (biochemistry / chemoproteomics)
Effect	PKM2 binds free methionine via a dedicated pocket and relays methionine availability to mTORC1 through GATOR2, independently of PKM2 enzymatic activity

In the Atlas

Links in the pathway map

Supports Methionine binds PKM2
Supports PKM2 inhibits GATOR2

Open questions that cite this study

Cited as supporting evidence for the open question Sensor-selective geroprotection without the metabolic penalty.

Cite this paper

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Sang, Z., Zheng, Y., Wang, X., Wu, C., Zhao, J., Wang, J. J., Sui, S., & Wang, J. (2026). "Trojan" Methionine Probe Reveals PKM2 as a Methionine-Sensing Protein in the mTORC1 Pathway. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.6c06772

@article{SANG2026,
  author       = {Sang, Z. and Zheng, Y. and Wang, X. and Wu, C. and Zhao, J. and Wang, J. J. and Sui, S. and Wang, J.},
  title        = {{"Trojan" Methionine Probe Reveals PKM2 as a Methionine-Sensing Protein in the mTORC1 Pathway}},
  journal      = {Journal of the American Chemical Society},
  year         = {2026},
  doi          = {10.1021/jacs.6c06772},
  note         = {PMID: 42677553},
}

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 SANG2026) [Data set]. https://mtor-atlas.org/study/SANG2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SANG2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SANG2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SANG2026/},
  doi          = {10.5281/zenodo.22059963}
}

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