Component

Protein kinase A

Independent biological entity. Read linked claims for experimental scope and context.

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. The PKA signaling pathway participated in DIM-mediated ERalpha activation.

    Protein kinase A → Human estrogen receptor alpha / ESR1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"}
    experimental_model
    Gene expression, chromatin, inhibitors and growth assays
    exposure
    DIM 10 versus 50 micromolar; estradiol absent
    limitations
    The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.
    nutrient_topic
    Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
    organism
    Human MCF-7 and T47D cells
    plain_language
    A kinase pathway connected exposure to receptor signaling.
    primary_references
    [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
    tissue_or_cell_type
    ERalpha and proliferation

    Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 623–634

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene expression, chromatin, inhibitors and growth assays · source_derived_draft · unverified_draft

    ### dim-pka-eralpha The PKA signaling pathway participated in DIM-mediated ERalpha activation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase pathway connected exposure to receptor signaling. organism: Human MCF-7 and T47D cells tissue_or_cell_type: ERalpha and proliferation experimental_model: Gene expression, chromatin, inhibitors and growth assays limitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter. exposure: DIM 10 versus 50 micromolar; estradiol absent evidence_span: {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"} [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
    Complete structured claim and evidence

  2. PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.

    Protein kinase A → Human cystic fibrosis transmembrane conductance regulator / CFTR source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"}
    experimental_model
    PKA phosphorylation and CFTR mutagenesis
    exposure
    Serines 660, 737, 795 and 813
    limitations
    Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human CFTR in cells
    plain_language
    A kinase switches the channel into a state that can respond to stimulation.
    primary_references
    [chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6
    tissue_or_cell_type
    CFTR regulatory domain

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 237–248

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PKA phosphorylation and CFTR mutagenesis · source_derived_draft · unverified_draft

    ### chloride-pka-cftr PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase switches the channel into a state that can respond to stimulation. organism: Human CFTR in cells tissue_or_cell_type: CFTR regulatory domain experimental_model: PKA phosphorylation and CFTR mutagenesis limitations: Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model. exposure: Serines 660, 737, 795 and 813 evidence_span: {"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"} [chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. PTH increases TRPV5 activity through cAMP-PKA-dependent phosphorylation at T709 in receptor/channel expression assays.

    Parathyroid hormone / PTH → TRPV5 source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    HEK293 expression, calcium uptake, FRET, patch clamp and TRPV5 mutagenesis
    limitations
    Response required strong intracellular calcium buffering; cultured-cell mechanism.
    nutrient_topic
    Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
    organism
    Heterologous HEK293 expression system
    plain_language
    PTH can increase calcium entry through TRPV5.
    primary_references
    [degroot2009] Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2723979/ DOI: 10.1681/ASN.2008080873
    tissue_or_cell_type
    Plasma membrane; distal-nephron mechanism

    Calcium: mechanism-first literature curation (2026-09-17) · lines 58–67

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 expression, calcium uptake, FRET, patch clamp and TRPV5 mutagenesis · source_derived_draft · unverified_draft

    ### pth-activates-trpv5 PTH increases TRPV5 activity through cAMP-PKA-dependent phosphorylation at T709 in receptor/channel expression assays. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: PTH can increase calcium entry through TRPV5. organism: Heterologous HEK293 expression system tissue_or_cell_type: Plasma membrane; distal-nephron mechanism experimental_model: HEK293 expression, calcium uptake, FRET, patch clamp and TRPV5 mutagenesis limitations: Response required strong intracellular calcium buffering; cultured-cell mechanism. [degroot2009] Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2723979/ DOI: 10.1681/ASN.2008080873
    Complete structured claim and evidence

  2. 6-Gingerol enhanced measured PKA activity in the stimulated human-neutrophil experiments.

    6-Gingerol → Protein kinase A activity in human neutrophils source_derived_draftungraded
    Experimental context and source evidence
    dose
    6-Gingerol 10 micromolar with forskolin or cAMP stimulation
    duration
    Kinase assay incubation 90 min; cellular pretreatment interval not resolved here
    evidence_access
    Primary open full text, results, figure legends and methods, plus PubMed metadata.
    evidence_scope
    literature_reviewed; model-specific source-derived curation, not universally established human effects
    experimental_model
    Neutrophils isolated from healthy human donors
    limitations
    Activity response, not demonstrated direct binding of gingerol to PKA.
    nutrient_topic
    Gingerols collection; each molecular form and experimental preparation remains explicit. · Gingerols
    organism
    Neutrophils isolated from healthy human donors
    plain_language
    6-Gingerol enhanced measured PKA activity in the stimulated human-neutrophil experiments.
    primary_references
    Antineutrophil properties of natural gingerols in models of lupus. (2021). https://pubmed.ncbi.nlm.nih.gov/33373329/ DOI: 10.1172/jci.insight.138385
    route
    Ex vivo exposure and lysate kinase assay
    tissue
    Human neutrophil PKA activity assay

    Gingerols: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 470–479

    Original AI-assisted curation of thirteen primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Neutrophils isolated from healthy human donors · source_derived_draft · unverified_draft

    ## gingerols-6-neutrophil-pka 6-Gingerol enhanced measured PKA activity in the stimulated human-neutrophil experiments. Model/species: Neutrophils isolated from healthy human donors Tissue: Human neutrophil PKA activity assay Exposure: 6-Gingerol 10 micromolar with forskolin or cAMP stimulation Route: Ex vivo exposure and lysate kinase assay Duration: Kinase assay incubation 90 min; cellular pretreatment interval not resolved here Limits: Activity response, not demonstrated direct binding of gingerol to PKA. Primary reference: Antineutrophil properties of natural gingerols in models of lupus. (2021). https://pubmed.ncbi.nlm.nih.gov/33373329/ DOI: 10.1172/jci.insight.138385 Access: Primary open full text, results, figure legends and methods, plus PubMed metadata.
    Complete structured claim and evidence

  3. Adding a PKA inhibitor weakened 6-gingerol suppression of APS-IgG-triggered NETosis in human neutrophils.

    Pharmacologically PKA-inhibited human neutrophil state → NET formation by human neutrophils source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    dose
    6-Gingerol with APS IgG and PKA inhibitor; exact inhibitor dose not specified in inspected text
    duration
    3 h NETosis assay
    evidence_access
    Primary open full text, results, figure legends and methods, plus PubMed metadata.
    evidence_scope
    literature_reviewed; model-specific source-derived curation, not universally established human effects
    experimental_model
    Human donor neutrophils with pharmacologically inhibited PKA
    limitations
    Supports a PKA-sensitive component; pharmacological inhibition is not selective genetic deletion or a nutrient deficiency.
    nutrient_topic
    Gingerols collection; each molecular form and experimental preparation remains explicit. · Gingerols
    organism
    Human donor neutrophils with pharmacologically inhibited PKA
    plain_language
    Adding a PKA inhibitor weakened 6-gingerol suppression of APS-IgG-triggered NETosis in human neutrophils.
    primary_references
    Antineutrophil properties of natural gingerols in models of lupus. (2021). https://pubmed.ncbi.nlm.nih.gov/33373329/ DOI: 10.1172/jci.insight.138385
    route
    Ex vivo co-exposure
    tissue
    Human neutrophils
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Gingerols: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 481–490

    Original AI-assisted curation of thirteen primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human donor neutrophils with pharmacologically inhibited PKA · source_derived_draft · unverified_draft

    ## gingerols-pka-blockade Adding a PKA inhibitor weakened 6-gingerol suppression of APS-IgG-triggered NETosis in human neutrophils. Model/species: Human donor neutrophils with pharmacologically inhibited PKA Tissue: Human neutrophils Exposure: 6-Gingerol with APS IgG and PKA inhibitor; exact inhibitor dose not specified in inspected text Route: Ex vivo co-exposure Duration: 3 h NETosis assay Limits: Supports a PKA-sensitive component; pharmacological inhibition is not selective genetic deletion or a nutrient deficiency. Primary reference: Antineutrophil properties of natural gingerols in models of lupus. (2021). https://pubmed.ncbi.nlm.nih.gov/33373329/ DOI: 10.1172/jci.insight.138385 Access: Primary open full text, results, figure legends and methods, plus PubMed metadata.
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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

    Evidence, AI assistance and curation standards