Component

STE20/SPS1-related proline/alanine-rich kinase

Canonical protein; experimental species, state, expression context and nutritional dependence are specified per claim.

9 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. SPAK phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation.

    STE20/SPS1-related proline/alanine-rich kinase → Thiazide-sensitive sodium-chloride cotransporter source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Defines the sodium/chloride transporter step of the potassium switch.
    evidence_location
    Primary abstract; phosphosite mapping, docking and Thr60Ala assays.
    experimental_model
    Recombinant phosphosite mapping and cell mutants
    limitations
    The dietary K response was not tested in this experiment.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Human protein; HEK293/mpkDCT cells
    plain_language
    A kinase modifies the sodium-chloride transporter at regulatory sites.
    primary_references
    [richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312
    tissue_or_cell_type
    Biochemical assay and cultured kidney-derived cells

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 164–175

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant phosphosite mapping and cell mutants · source_derived_draft · unverified_draft

    ### renal-stk39-phosphorylates-ncc SPAK phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase modifies the sodium-chloride transporter at regulatory sites. organism: Human protein; HEK293/mpkDCT cells tissue_or_cell_type: Biochemical assay and cultured kidney-derived cells experimental_model: Recombinant phosphosite mapping and cell mutants limitations: The dietary K response was not tested in this experiment. cross_nutrient: Defines the sodium/chloride transporter step of the potassium switch. evidence_location: Primary abstract; phosphosite mapping, docking and Thr60Ala assays. [richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312
    Complete structured claim and evidence

What acts on it

  1. Catalytically active WNK4 phosphorylated and activated SPAK in biochemical assays.

    WNK lysine deficient protein kinase 4 → STE20/SPS1-related proline/alanine-rich kinase source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    This kinase relay can regulate sodium/chloride transport downstream of K sensing.
    evidence_location
    Primary abstract; kinase-activity and substrate-phosphorylation experiments.
    experimental_model
    Recombinant kinase assay
    limitations
    Establishes biochemical capability; not dietary potassium regulation by itself.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Recombinant proteins
    plain_language
    WNK4 passes a phosphate signal to SPAK.
    primary_references
    [vitari-2005-wnk-spak-osr1] The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases (2005). https://pubmed.ncbi.nlm.nih.gov/16083423/ DOI: 10.1042/BJ20051180
    tissue_or_cell_type
    Cell-free assay

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 151–162

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

    ### renal-wnk4-activates-spak Catalytically active WNK4 phosphorylated and activated SPAK in biochemical assays. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: WNK4 passes a phosphate signal to SPAK. organism: Recombinant proteins tissue_or_cell_type: Cell-free assay experimental_model: Recombinant kinase assay limitations: Establishes biochemical capability; not dietary potassium regulation by itself. cross_nutrient: This kinase relay can regulate sodium/chloride transport downstream of K sensing. evidence_location: Primary abstract; kinase-activity and substrate-phosphorylation experiments. [vitari-2005-wnk-spak-osr1] The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases (2005). https://pubmed.ncbi.nlm.nih.gov/16083423/ DOI: 10.1042/BJ20051180
    Complete structured claim and evidence

Where it participates (unsigned role)

  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

  2. 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

  3. OSR1/SPAK activation inhibited CFTR-dependent chloride/bicarbonate exchange in the tested system.

    Oxidative stress responsive kinase 1 → Pancreatic CFTR-dependent chloride/bicarbonate exchange activity 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 same signaling program reduced an exchange route that could take bicarbonate back from the secretion.
    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 289–300

    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-exchange OSR1/SPAK activation inhibited CFTR-dependent chloride/bicarbonate exchange in the tested system. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same signaling program reduced an exchange route that could take bicarbonate back from the secretion. 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

  4. Increasing chloride inhibited recombinant WNK4 phosphorylation of SPAK more strongly than WNK1/3 in matched assays.

    Chloride ion → WNK lysine deficient protein kinase 4 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Chloride concentration gates a kinase linking K sensing to Na transport.
    evidence_location
    Figure 3; equimolar chloride/gluconate kinase assay.
    experimental_model
    Purified kinase domains; SPAK substrate
    limitations
    Does not directly measure native DCT chloride or WNK4 autophosphorylation.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Recombinant proteins
    plain_language
    Chloride restrains WNK4, a kinase upstream of sodium-chloride transport.
    primary_references
    [terker-2016-wnk4-chloride] Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4814375/ DOI: 10.1038/ki.2015.289
    tissue_or_cell_type
    Cell-free assay

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 138–149

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

    ### renal-chloride-inhibits-wnk4 Increasing chloride inhibited recombinant WNK4 phosphorylation of SPAK more strongly than WNK1/3 in matched assays. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride restrains WNK4, a kinase upstream of sodium-chloride transport. organism: Recombinant proteins tissue_or_cell_type: Cell-free assay experimental_model: Purified kinase domains; SPAK substrate limitations: Does not directly measure native DCT chloride or WNK4 autophosphorylation. cross_nutrient: Chloride concentration gates a kinase linking K sensing to Na transport. evidence_location: Figure 3; equimolar chloride/gluconate kinase assay. [terker-2016-wnk4-chloride] Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4814375/ DOI: 10.1038/ki.2015.289
    Complete structured claim and evidence

  5. High-K-induced NCC dephosphorylation persisted during low extracellular chloride or chloride-channel blockade in mouse kidney preparations.

    Potassium ion → NCC phosphorylation source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    High K can suppress the sodium/chloride transporter through additional signaling.
    evidence_location
    Primary abstract; low extracellular chloride and DIDS experiments.
    experimental_model
    Perfused kidney and kidney slices
    limitations
    Pharmacological/ionic tests do not prove every chloride-sensitive step is absent.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Mus musculus
    plain_language
    The rapid high-potassium response can persist when tested chloride movements are disrupted.
    primary_references
    [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504
    tissue_or_cell_type
    Native DCT

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 229–240

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

    ### renal-native-high-k-cl-independent-ncc-off High-K-induced NCC dephosphorylation persisted during low extracellular chloride or chloride-channel blockade in mouse kidney preparations. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The rapid high-potassium response can persist when tested chloride movements are disrupted. organism: Mus musculus tissue_or_cell_type: Native DCT experimental_model: Perfused kidney and kidney slices limitations: Pharmacological/ionic tests do not prove every chloride-sensitive step is absent. cross_nutrient: High K can suppress the sodium/chloride transporter through additional signaling. evidence_location: Primary abstract; low extracellular chloride and DIDS experiments. [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504
    Complete structured claim and evidence

  6. In native mouse kidney preparations, low extracellular K increased NCC phosphorylation through chloride-conductance-dependent SPAK/OSR1 signaling.

    Potassium ion → NCC phosphorylation source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    K concentration regulates sodium/chloride transport via chloride-sensitive signaling.
    evidence_location
    Abstract and Results; low chloride and DIDS comparisons.
    experimental_model
    Perfused kidney and kidney slices
    limitations
    Acute bath/perfusate manipulation is not whole-body potassium depletion.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Mus musculus
    plain_language
    The low-potassium signal needs chloride movement to increase the transporter phosphate signal.
    primary_references
    [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504
    tissue_or_cell_type
    Native DCT

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 216–227

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

    ### renal-native-low-k-requires-chloride-flux In native mouse kidney preparations, low extracellular K increased NCC phosphorylation through chloride-conductance-dependent SPAK/OSR1 signaling. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The low-potassium signal needs chloride movement to increase the transporter phosphate signal. organism: Mus musculus tissue_or_cell_type: Native DCT experimental_model: Perfused kidney and kidney slices limitations: Acute bath/perfusate manipulation is not whole-body potassium depletion. cross_nutrient: K concentration regulates sodium/chloride transport via chloride-sensitive signaling. evidence_location: Abstract and Results; low chloride and DIDS comparisons. [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504
    Complete structured claim and evidence

  7. Chloride-insensitive WNK4 blocked high-K NCC dephosphorylation in HEK cells; the authors inferred that WNK4-SPAK inhibition is required for the rapid response.

    WNK4 L319F/L321F chloride-insensitive variant → NCC phosphorylation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Balance of kinase and phosphatase signaling controls Na/Cl transport responses to K.
    evidence_location
    Discussion; WNK4-LLFF HEK experiment and acute-versus-prolonged restriction comparison.
    experimental_model
    HEK mutant expression with complementary mouse/kidney-slice experiments
    limitations
    Inference about obligatory kinase shutdown is disputed; model and adaptation time matter.
    nutrient_topic
    Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
    organism
    Homo sapiens cell line; Mus musculus
    plain_language
    A strongly active kinase relay can keep NCC phosphorylated during an acute potassium challenge.
    primary_references
    [yang-2021-ncc-off-switch] Roles of WNK4 and SPAK in K+-mediated dephosphorylation of the NaCl cotransporter (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8174808/ DOI: 10.1152/ajprenal.00459.2020
    tissue_or_cell_type
    HEK cells and renal DCT
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 255–266

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK mutant expression with complementary mouse/kidney-slice experiments · source_derived_draft · unverified_draft

    ### renal-wnk4-spak-activation-opposes-acute-off Chloride-insensitive WNK4 blocked high-K NCC dephosphorylation in HEK cells; the authors inferred that WNK4-SPAK inhibition is required for the rapid response. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A strongly active kinase relay can keep NCC phosphorylated during an acute potassium challenge. organism: Homo sapiens cell line; Mus musculus tissue_or_cell_type: HEK cells and renal DCT experimental_model: HEK mutant expression with complementary mouse/kidney-slice experiments limitations: Inference about obligatory kinase shutdown is disputed; model and adaptation time matter. cross_nutrient: Balance of kinase and phosphatase signaling controls Na/Cl transport responses to K. evidence_location: Discussion; WNK4-LLFF HEK experiment and acute-versus-prolonged restriction comparison. [yang-2021-ncc-off-switch] Roles of WNK4 and SPAK in K+-mediated dephosphorylation of the NaCl cotransporter (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8174808/ DOI: 10.1152/ajprenal.00459.2020
    Complete structured claim and evidence

In the sources

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

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