Phosphorylation of AMP-activated protein kinase at threonine 172: molecular mechanisms & dependencies

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What it does

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Recorded relationships

Where it participates (unsigned role)

Intracellular salicylate concentrations increased within five minutes in both rat fast-twitch and slow-twitch muscle, threonine-172 phosphorylation of the AMP-activated protein kinase alpha subunit increased dose- and time-dependently with increases in both alpha-1 and alpha-2 activity, and these were accompanied by increased 3-O-methyl-D-glucose transport and decreases in ATP, phosphocreatine and glycogen, while phosphorylation of insulin receptor substrate 1, Akt and p70 S6 kinase was unchanged.
Salicylate / salicylic acid → Insulin-independent glucose transport in skeletal muscle source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/aspirin-research/25256746.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8cd347665e1de7dc2cadee06da087e2526d4fc11aefef6f7ce15cb33f6234c2", "start_char": 0, "end_char": 1171, "text_sha256": "e8cd347665e1de7dc2cadee06da087e2526d4fc11aefef6f7ce15cb33f6234c2"}
experimental_model
Incubation of rat fast-twitch epitrochlearis and slow-twitch soleus muscle with salicylate
exposure
Salicylate applied to isolated muscle with glucose transport and nucleotide measurements
limitations
Adds the tissue and the energy measurements. Isolated muscle at concentrations set by the incubation buffer, which is not a plasma concentration.
nutrient_topic
Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid
organism
Rat
plain_language
Muscle takes up more glucose without any help from insulin, and its energy stores fall while it happens.
primary_references
[asa-p25256746] Salicylate acutely stimulates 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscles. (2014). https://pubmed.ncbi.nlm.nih.gov/25256746/ DOI: 10.1016/j.bbrc.2014.09.066
tissue_or_cell_type
Skeletal muscle
trigger_kind
biomarker_context Imported condition classification; unverified.
Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 507–518
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Incubation of rat fast-twitch epitrochlearis and slow-twitch soleus muscle with salicylate · source_derived_draft · unverified_draft
### asa-muscle-glucose-uptake Intracellular salicylate concentrations increased within five minutes in both rat fast-twitch and slow-twitch muscle, threonine-172 phosphorylation of the AMP-activated protein kinase alpha subunit increased dose- and time-dependently with increases in both alpha-1 and alpha-2 activity, and these were accompanied by increased 3-O-methyl-D-glucose transport and decreases in ATP, phosphocreatine and glycogen, while phosphorylation of insulin receptor substrate 1, Akt and p70 S6 kinase was unchanged. Condition category: biomarker_context nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Muscle takes up more glucose without any help from insulin, and its energy stores fall while it happens. organism: Rat tissue_or_cell_type: Skeletal muscle experimental_model: Incubation of rat fast-twitch epitrochlearis and slow-twitch soleus muscle with salicylate limitations: Adds the tissue and the energy measurements. Isolated muscle at concentrations set by the incubation buffer, which is not a plasma concentration. exposure: Salicylate applied to isolated muscle with glucose transport and nucleotide measurements evidence_span: {"source_cache": "artifacts/aspirin-research/25256746.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8cd347665e1de7dc2cadee06da087e2526d4fc11aefef6f7ce15cb33f6234c2", "start_char": 0, "end_char": 1171, "text_sha256": "e8cd347665e1de7dc2cadee06da087e2526d4fc11aefef6f7ce15cb33f6234c2"} [asa-p25256746] Salicylate acutely stimulates 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscles. (2014). https://pubmed.ncbi.nlm.nih.gov/25256746/ DOI: 10.1016/j.bbrc.2014.09.066
Complete structured claim and evidence
At concentrations reached in plasma after administration of salsalate or of aspirin at high doses, salicylate activates AMP-activated protein kinase by binding at the same site as the synthetic activator A-769662 to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site threonine-172, and in knockout mice the effects of salicylate to increase fat utilisation and to lower plasma fatty acids in vivo were lost.
Salicylate / salicylic acid → AMP-activated protein kinase complexes source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/aspirin-research/22517326.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a48863bf252421416f67d62acb18c9f44f170075c5aff6f775eba14bba2b1b4", "start_char": 0, "end_char": 887, "text_sha256": "1a48863bf252421416f67d62acb18c9f44f170075c5aff6f775eba14bba2b1b4"}
experimental_model
Allosteric activation and dephosphorylation assays with AMP-activated protein kinase knockout mice
exposure
Salicylate at concentrations reached in plasma after salsalate or high-dose aspirin, against the synthetic activator A-769662
limitations
The knockout arm ties the whole-animal effect to the kinase. The concentrations are those of high-dose salicylate therapy, not of antiplatelet aspirin, which the authors state explicitly.
nutrient_topic
Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid
organism
Human enzyme and mouse
plain_language
The old plant compound switches on the cell’s energy sensor directly, at doses far above a daily aspirin.
primary_references
[asa-p22517326] The ancient drug salicylate directly activates AMP-activated protein kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/22517326/ DOI: 10.1126/science.1215327
tissue_or_cell_type
AMP-activated protein kinase
trigger_kind
biomarker_context Imported condition classification; unverified.
Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 494–505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Allosteric activation and dephosphorylation assays with AMP-activated protein kinase knockout mice · source_derived_draft · unverified_draft
### asa-salicylate-activates-ampk At concentrations reached in plasma after administration of salsalate or of aspirin at high doses, salicylate activates AMP-activated protein kinase by binding at the same site as the synthetic activator A-769662 to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site threonine-172, and in knockout mice the effects of salicylate to increase fat utilisation and to lower plasma fatty acids in vivo were lost. Condition category: biomarker_context nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The old plant compound switches on the cell’s energy sensor directly, at doses far above a daily aspirin. organism: Human enzyme and mouse tissue_or_cell_type: AMP-activated protein kinase experimental_model: Allosteric activation and dephosphorylation assays with AMP-activated protein kinase knockout mice limitations: The knockout arm ties the whole-animal effect to the kinase. The concentrations are those of high-dose salicylate therapy, not of antiplatelet aspirin, which the authors state explicitly. exposure: Salicylate at concentrations reached in plasma after salsalate or high-dose aspirin, against the synthetic activator A-769662 evidence_span: {"source_cache": "artifacts/aspirin-research/22517326.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a48863bf252421416f67d62acb18c9f44f170075c5aff6f775eba14bba2b1b4", "start_char": 0, "end_char": 887, "text_sha256": "1a48863bf252421416f67d62acb18c9f44f170075c5aff6f775eba14bba2b1b4"} [asa-p22517326] The ancient drug salicylate directly activates AMP-activated protein kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/22517326/ DOI: 10.1126/science.1215327
Complete structured claim and evidence

The events it takes part in

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In the sources

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Open hypotheses

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This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

Phosphorylation of AMP-activated protein kinase at threonine 172