{
 "meta": {
  "api_version": "1.0.0",
  "dataset_version": "2.0.1+unreleased",
  "live_matches_release": false,
  "archived_release": {
   "version": "2.0.1",
   "version_doi": "10.5281/zenodo.23090261",
   "date": "2026-10-01",
   "studies": 428
  },
  "data_fingerprint": "4823f516b720e66843f0b75952daf5ccc5279a7c20c0cb7c0d1ac126ff6ca768",
  "corpus_snapshot": "2026-10-24T21:34:23+0200",
  "source_commit": "8f0f14a10e115daab72bb59e5bf8c63eda1daeb8",
  "license": "CC-BY-4.0",
  "cite": "Barton O. Oliver's mTOR Atlas (live data, not an archived version; give corpus_snapshot and source_commit). doi:10.5281/zenodo.22059963",
  "docs": "https://mtor-atlas.org/api/"
 },
 "data": {
  "id": "S6K1-IRS1",
  "claim": "S6K1 inhibits IRS-1 / IRS-2",
  "source": {
   "name": "S6K1",
   "entity": "s6k1"
  },
  "target": {
   "name": "IRS-1 / IRS-2",
   "entity": "irs-1-irs-2"
  },
  "effect": "inhibits",
  "type": "degradation",
  "directness": "direct",
  "timescale": "hours",
  "compartment": "cytosol",
  "map_band": "cytosol",
  "species": [
   "mammalian cells"
  ],
  "mechanism": "One of the pathway's major negative feedback loops, and the best studied. Sustained S6K1 activity, as in obesity and nutrient excess, phosphorylates IRS-1 and represses its expression, so the insulin receptor can no longer signal to PI3K. This is a major reason blocking mTORC1 paradoxically RAISES Akt activity (the Grb10 arm adds to it). Rapalog-associated insulin resistance runs mainly through a different route, disruption of mTORC2 (LAM2012, in mice).",
  "mechanism_beginner": "This is one of the pathway's main self-limiting \"off switches\": strong, sustained S6K1 activity shuts down IRS-1, cutting the insulin signal off. That is how too much food can blunt the insulin signal. It also runs the other way: block mTOR and IRS-1 survives, so Akt can paradoxically become MORE active – which is why the insulin resistance seen on these drugs is blamed, on evidence from mice, on a different mechanism (loss of mTORC2), not on this loop.",
  "context": null,
  "boundary": "Established in cells and mouse genetics. The size of this arm's contribution to rapalog dysglycaemia in humans, relative to mTORC2 loss, has not been apportioned.",
  "boundary_tags": [],
  "note": "Added 2026-07-29 after external review found this canonical loop missing from the graph.",
  "consensus_contested": false,
  "curation_contested": false,
  "contested": false,
  "confidence": {
   "mechanistic": "high",
   "human_relevance": "plausible",
   "consensus": "established"
  },
  "evidence": {
   "kind": "Direct biochemical",
   "strongest": {
    "code": "A",
    "label": "Animal model"
   },
   "supporting": [
    "HAR2004",
    "SHA2004",
    "UMX2004",
    "ORE2006"
   ],
   "conflicting": []
  },
  "external_refs": [],
  "reviewed": null,
  "updated": null,
  "checked": null,
  "review_status": "unreviewed",
  "reviewer": null,
  "curation_status": "Proposed",
  "url": "https://mtor-atlas.org/relation/S6K1-IRS1/",
  "api_url": "https://mtor-atlas.org/api/v1/relations/S6K1-IRS1.json"
 }
}