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"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 type5 - Mechanistic / In Vitro
Model systemHuman cells (chemoproteomics / photoaffinity probe)
JournalJournal of the American Chemical Society
Year2026
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1021/jacs.6c06772 · PMID 42677553

Extracted findings

InterventionPhotoaffinity methionine analogue (chemoproteomic capture); methionine restriction/repletion
TargetPKM2 / GATOR2 / mTORC1 (methionine sensing)
ModelHuman cells (biochemistry / chemoproteomics)
EffectPKM2 binds free methionine via a dedicated pocket and relays methionine availability to mTORC1 through GATOR2, independently of PKM2 enzymatic activity

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}
}