Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms

Shen K, Sabatini DM · 2018 · Proceedings of the National Academy of Sciences of the United States of America · Atlas ID SHE2018B

What this study shows

Ragulator and SLC38A9 each act as an unusual guanine-nucleotide exchange factor on the Rag heterodimer, and together they push it into its active state. Ragulator triggers GTP release from RagC, which unlocks the inactive configuration; arginine-bound SLC38A9 converts RagA from the GDP- to the GTP-loaded state. Boundary: purified proteins and cultured human cells. This is the biochemistry of the switch, not a measurement in tissue.

Abstract

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The mechanistic target of rapamycin complex 1 (mTORC1) growth pathway detects nutrients through a variety of sensors and regulators that converge on the Rag GTPases, which form heterodimers consisting of RagA or RagB tightly bound to RagC or RagD and control the subcellular localization of mTORC1. The Rag heterodimer uses a unique "locking" mechanism to stabilize its active (RagA(GTP)-RagC(GDP)) or inactive (RagA(GDP)-RagC(GTP)) nucleotide states.

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: Purified recombinant proteins; HEK293 cells) 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	Purified recombinant proteins; HEK293 cells
Journal	Proceedings of the National Academy of Sciences of the United States of America
Year	2018
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1073/pnas.1811727115 · PMID 30181260 · Free full text (PMC6156610)

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	Biochemical nucleotide-exchange assays (Ragulator, SLC38A9)
Target	Ragulator / SLC38A9 / Rag GTPases / mTORC1
Model	Purified proteins; human cells (HEK293)
Effect	Ragulator releases GTP from RagC and arginine-bound SLC38A9 loads RagA with GTP; together they activate the Rag heterodimer

In the Atlas

Links in the pathway map

Supports Ragulator activates Rag GTPases
Supports SLC38A9 activates Rag GTPases

Cite this paper

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Shen, K., & Sabatini, D. M. (2018). Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1811727115

@article{SHE2018B,
  author       = {Shen, K. and Sabatini, D. M.},
  title        = {{Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms}},
  journal      = {Proceedings of the National Academy of Sciences of the United States of America},
  year         = {2018},
  doi          = {10.1073/pnas.1811727115},
  note         = {PMID: 30181260},
}

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 SHE2018B) [Data set]. https://mtor-atlas.org/study/SHE2018B/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SHE2018B,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SHE2018B},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SHE2018B/},
  doi          = {10.5281/zenodo.22059963}
}

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