Component
WNK lysine deficient protein kinase 4
Canonical protein; experimental species, state, expression context and nutritional dependence are specified per claim.
4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
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.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
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.
What it acts on
Catalytically active WNK4 phosphorylated and activated SPAK in biochemical assays.
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
What acts on it
Increasing chloride inhibited recombinant WNK4 phosphorylation of SPAK more strongly than WNK1/3 in matched assays.
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
Where it participates (unsigned role)
Acute oral potassium failed to suppress NCC in mice carrying chloride-insensitive WNK4, unlike wild-type controls.
Experimental context and source evidence
- availability_state
- machinery_impairment Imported condition classification; unverified.
- cross_nutrient
- A chloride-sensing defect disrupts K control of sodium transport.
- evidence_location
- Primary abstract; acute gavage NCC comparison.
- experimental_model
- Wnk4 LLFF knockin; oral K gavage
- limitations
- Constitutive kinase activation and longer-term K responses must be distinguished.
- nutrient_topic
- Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
- organism
- Mus musculus
- plain_language
- Making WNK4 insensitive to chloride blocks the rapid potassium response in this mouse model.
- primary_references
- [chen-2019-wnk4-sensor] WNK4 kinase is a physiological intracellular chloride sensor (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6410802/ DOI: 10.1073/pnas.1817220116
- tissue_or_cell_type
- Kidney DCT
- trigger_kind
- machinery_impairment Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 242–253
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wnk4 LLFF knockin; oral K gavage · source_derived_draft · unverified_draft
### renal-wnk4-chloride-mutant-blocks-acute-k-off Acute oral potassium failed to suppress NCC in mice carrying chloride-insensitive WNK4, unlike wild-type controls. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making WNK4 insensitive to chloride blocks the rapid potassium response in this mouse model. organism: Mus musculus tissue_or_cell_type: Kidney DCT experimental_model: Wnk4 LLFF knockin; oral K gavage limitations: Constitutive kinase activation and longer-term K responses must be distinguished. cross_nutrient: A chloride-sensing defect disrupts K control of sodium transport. evidence_location: Primary abstract; acute gavage NCC comparison. [chen-2019-wnk4-sensor] WNK4 kinase is a physiological intracellular chloride sensor (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6410802/ DOI: 10.1073/pnas.1817220116
Complete structured claim and evidenceChloride-insensitive WNK4 blocked high-K NCC dephosphorylation in HEK cells; the authors inferred that WNK4-SPAK inhibition is required for the rapid response.
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
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.