Component

Human WNK lysine deficient protein kinase 1 / WNK1

Human WNK lysine deficient protein kinase 1 / WNK1. Species, exposure and limitations are retained in each linked claim.

6 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. WNK1-mediated OSR1/SPAK activation increased CFTR bicarbonate permeability.

    Human WNK lysine deficient protein kinase 1 / WNK1 → CFTR bicarbonate permeability source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}
    experimental_model
    Expression, duct-cell and pancreatic-tissue experiments
    exposure
    Low intracellular chloride; WNK1–OSR1/SPAK activation
    limitations
    Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human and guinea pig
    plain_language
    The channel became better at carrying bicarbonate for alkaline pancreatic fluid.
    primary_references
    [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
    tissue_or_cell_type
    Pancreatic duct

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 276–287

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft

    ### chloride-pancreatic-bicarbonate WNK1-mediated OSR1/SPAK activation increased CFTR bicarbonate permeability. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The channel became better at carrying bicarbonate for alkaline pancreatic fluid. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
    Complete structured claim and evidence

What acts on it

  1. Lower intracellular chloride activated the WNK1–OSR1/SPAK pathway in the pancreatic experiments.

    Intracellular chloride concentration → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}
    experimental_model
    Expression, duct-cell and pancreatic-tissue experiments
    exposure
    Low intracellular chloride; WNK1–OSR1/SPAK activation
    limitations
    Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human and guinea pig
    plain_language
    A fall in chloride inside a duct cell can switch its secretory program.
    primary_references
    [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
    tissue_or_cell_type
    Pancreatic duct

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 263–274

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft

    ### chloride-pancreatic-cl-signal Lower intracellular chloride activated the WNK1–OSR1/SPAK pathway in the pancreatic experiments. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A fall in chloride inside a duct cell can switch its secretory program. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
    Complete structured claim and evidence

  2. Chloride bound the WNK1 catalytic region and stabilized its inactive conformation.

    Chloride ion → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"}
    experimental_model
    Crystallography and kinase mutagenesis
    exposure
    Chloride binding and chloride-pocket mutants
    limitations
    Cell-free sensing; plasma chloride is not identical to kinase-site chloride.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human WNK1 kinase constructs
    plain_language
    Chloride can act as a direct signal to a kinase, not just as an accompanying ion.
    primary_references
    [chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050
    tissue_or_cell_type
    Purified kinase domain

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 315–326

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

    ### chloride-wnk1-binding Chloride bound the WNK1 catalytic region and stabilized its inactive conformation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride can act as a direct signal to a kinase, not just as an accompanying ion. organism: Human WNK1 kinase constructs tissue_or_cell_type: Purified kinase domain experimental_model: Crystallography and kinase mutagenesis limitations: Cell-free sensing; plasma chloride is not identical to kinase-site chloride. exposure: Chloride binding and chloride-pocket mutants evidence_span: {"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"} [chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050
    Complete structured claim and evidence

  3. Chloride inhibited WNK1 autophosphorylation; binding-site mutations reduced this inhibition.

    Chloride ion → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"}
    experimental_model
    Crystallography and kinase mutagenesis
    exposure
    Chloride binding and chloride-pocket mutants
    limitations
    Cell-free sensing; plasma chloride is not identical to kinase-site chloride.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human WNK1 kinase constructs
    plain_language
    When the chloride brake is released, this kinase can activate itself.
    primary_references
    [chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050
    tissue_or_cell_type
    Purified kinase domain

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 328–339

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

    ### chloride-wnk1-inhibition Chloride inhibited WNK1 autophosphorylation; binding-site mutations reduced this inhibition. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: When the chloride brake is released, this kinase can activate itself. organism: Human WNK1 kinase constructs tissue_or_cell_type: Purified kinase domain experimental_model: Crystallography and kinase mutagenesis limitations: Cell-free sensing; plasma chloride is not identical to kinase-site chloride. exposure: Chloride binding and chloride-pocket mutants evidence_span: {"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"} [chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050
    Complete structured claim and evidence

  4. Chloride opposed osmolyte-stimulated WNK1 autophosphorylation.

    Chloride ion → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"}
    experimental_model
    Biochemistry and structural measurements
    exposure
    PEG400 or ethylene glycol osmotic challenge
    limitations
    Artificial osmolytes; supports additional regulation, not a universal chloride-only switch.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human WNK1 and WNK3 constructs
    plain_language
    Water balance and chloride jointly influence the kinase.
    primary_references
    [chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089
    tissue_or_cell_type
    Purified kinase domains

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 341–352

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemistry and structural measurements · source_derived_draft · unverified_draft

    ### chloride-wnk1-osmotic Chloride opposed osmolyte-stimulated WNK1 autophosphorylation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Water balance and chloride jointly influence the kinase. organism: Human WNK1 and WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Biochemistry and structural measurements limitations: Artificial osmolytes; supports additional regulation, not a universal chloride-only switch. exposure: PEG400 or ethylene glycol osmotic challenge evidence_span: {"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"} [chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089
    Complete structured claim and evidence

  5. WNK1 E388 mutations reduced potassium inhibition while retaining kinase activity.

    Potassium ion → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/42186973.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa", "start_char": 0, "end_char": 1266, "text_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa"}
    experimental_model
    Crystallography and mutagenesis
    exposure
    Cesium surrogate and potassium-inhibition assays
    limitations
    Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human WNK1/WNK3 constructs
    plain_language
    Potassium can regulate WNK1 directly as well as through changes in cell voltage and chloride.
    primary_references
    [chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825
    tissue_or_cell_type
    Purified kinase domains

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 367–378

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

    ### chloride-wnk1-potassium WNK1 E388 mutations reduced potassium inhibition while retaining kinase activity. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium can regulate WNK1 directly as well as through changes in cell voltage and chloride. organism: Human WNK1/WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Crystallography and mutagenesis limitations: Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing. exposure: Cesium surrogate and potassium-inhibition assays evidence_span: {"source_cache": "artifacts/chloride-research/42186973.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa", "start_char": 0, "end_char": 1266, "text_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa"} [chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825
    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