Cells carry their own growth switches. When enough nutrients—amino acids in particular—are available, cells flip this switch on and begin to grow. Researchers at KAIST and Yonsei University have uncovered the molecular mechanism by which amino acid signals activate this cellular growth switch. The findings are expected to open a new avenue for anticancer therapies that target abnormal growth signaling in tumor cells.
The research team led by professors Hee-Sung Park and Jin Young Kang from the Department of Chemistry, working with Professor Sunghoon Kim's team from Yonsei University, has identified a molecular mechanism that links amino acid stimulation to mTORC1-dependent growth signaling.
The work is published in the journal Nature Communications.
The growth switch in cancer
Cells continually monitor whether enough amino acids—the basic building blocks of proteins—are available in their surroundings and adjust their growth, protein synthesis and energy use accordingly. Central to this process is mTORC1 (mammalian target of rapamycin complex 1), a protein complex that functions as the cell's growth switch.
mTORC1 promotes cell growth, protein synthesis and metabolism when nutrients and energy are abundant. But when mTORC1 becomes excessively active, cells can grow and proliferate beyond what is needed—a pattern of dysregulation observed in numerous cancers.
For this reason, mTORC1 has long been considered a prime target for anticancer drug development. Exactly how cells detect external nutrient cues and translate them into mTORC1 activation, however, has remained incompletely understood.
How LARS1 is released
The research team focused on the multi-tRNA synthetase complex (MSC), a large protein assembly composed of multiple aminoacyl-tRNA synthetases and scaffold proteins.
While aminoacyl-tRNA synthetases are best known for their essential role in protein synthesis—attaching specific amino acids to their cognate tRNAs—the team showed that, in response to amino acid stimulation, the MSC releases LARS1, thereby linking nutrient availability to growth signaling.
The key player within the MSC turned out to be a protein called LARS1 (leucyl-tRNA synthetase 1), an enzyme that attaches leucine to its corresponding tRNA and also functions as an intracellular leucine sensor. When cells receive a signal that nutrients are sufficient, LARS1 undergoes phosphorylation—a modification in which a small chemical tag is attached to a protein, altering its function or binding behavior.
The relationship can be pictured this way: The MSC is a control center where multiple proteins wait on standby, and LARS1 is the field agent dispatched to flip on the growth switch. When nutrients become abundant, LARS1 receives a phosphorylation "deployment signal," dissociates from IARS1, the protein that anchors LARS1 to the MSC, and is thereby released from the complex. The freed LARS1 then activates mTORC1.
In other words, when nutrients are scarce, LARS1 stays bound within the MSC and the growth signal remains off. Once nutrients become sufficient, LARS1 is released from the MSC and switches on mTORC1.
Cryo-EM reveals the binding change
To investigate the structural basis of this process, the team used cryo-electron microscopy (cryo-EM), a technique that visualizes protein complexes in three dimensions at near-atomic resolution by rapidly freezing samples at extremely low temperatures. This allowed the researchers to determine how LARS1 and IARS1 bind to each other and structurally explain how phosphorylation could disrupt their interaction.
The results showed that LARS1 and IARS1 are normally tightly bound, but amino acid stimulation induces the phosphorylation of LARS1, weakening its interaction with IARS1. This allows LARS1 to dissociate from the MSC and activate mTORC1.
The researchers also engineered phosphomimetic LARS1 variants—mutant proteins designed to imitate the phosphorylated state—and found that these variants substantially enhanced mTORC1 activity. This confirmed that the phosphorylation of LARS1 functions as the key molecular switch converting a nutrient signal into a cell growth signal.
A more precise drug target
The significance of this study lies in mapping, in concrete molecular detail, how cells sense amino acids and use that information to activate their growth switch. In particular, the study revealed that, upon receiving nutrient signals, the MSC—a complex involved in protein synthesis—releases its constituent protein LARS1, which then activates cellular growth signaling.
Some existing anticancer drugs work by directly inhibiting mTORC1, the cell's growth switch. However, because mTORC1 is also required for normal cellular growth and metabolism, its direct inhibition may also affect normal cells.
The research team expects that further identification of the kinase responsible for phosphorylating LARS1, along with its regulatory mechanism, could enable a more precise anticancer strategy—one that intercepts the growth signal further upstream, before it reaches mTORC1, rather than blocking mTORC1 itself.
Publication details
Youjin Kim et al, Cryo-EM structure of the LARS1:IARS1 complex reveals a nutrient-responsive switch controlling mTORC1 signaling, Nature Communications (2026). DOI: 10.1038/s41467-026-74085-x
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Citation: Molecular switch that activates cell growth signaling may offer more precise route for anticancer therapy (2026, July 27) retrieved 28 July 2026 from https://phys.org/news/2026-07-molecular-cell-growth-precise-route.html
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