ArticleProceedings of the National Academy of Sciences of the United States of America2007
SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Neuronal Sik1 in the Hypothalamic Paraventricular Nucleus Decreases Blood pressure Elevation Following a High-Salt Diet.Molecular neurobiology · 2026Article
- Salt-inducible Kinase Regulation of Adipose Tissue Metabolism.Endocrinology · 2025Review
- Salt-inducible kinases transduce mechanical forces into the specification of the pancreatic endocrine lineage.Stem cell reports · 2025Article
- Identification of a Novel QTL on LG16 Associated with Acute Salt Tolerance in Red Tilapia (Oreochromis spp.) Using GWAS.Marine biotechnology (New York, N.Y.) · 2025Article
- SIK1 Downregulates Synaptic AMPA Receptors and Contributes to Cognitive Defects in Alzheimer's Disease.Molecular neurobiology · 2024Article
- Role of SIK1 in tumors: Emerging players and therapeutic potentials (Review).Oncology reports · 2024Review
- Adrenocorticotropic hormone combined with magnesium sulfate therapy for infantile epileptic spasms syndrome: a real-world study.World journal of pediatrics : WJP · 2024Article
- Understanding the roles of salt-inducible kinases in cardiometabolic disease.Frontiers in physiology · 2024Review
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Sodium channels and the ionic microenvironment of breast tumours.The Journal of physiology · 2023Article
- The Triad NaInternational journal of molecular sciences · 2023Article
- High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)Annals of translational medicine · 2022Article
- Airway inflammation induces anxiety-like behavior through neuroinflammatory, neurochemical, and neurometabolic changes in an allergic asthma model.Metabolic brain disease · 2022Article
- Nuts and bolts of the salt-inducible kinases (SIKs).The Biochemical journal · 2021Review
- Salt Sensation and Regulation.Metabolites · 2021Review
- Effects of carboxyl-terminal methylation on holoenzyme function of the PP2A subfamily.Biochemical Society transactions · 2020Review
- The potent roles of salt-inducible kinases (SIKs) in metabolic homeostasis and tumorigenesis.Signal transduction and targeted therapy · 2020Review
- MicroRNA-132 regulates salt-dependent steady-state renin levels in mice.Communications biology · 2020Article
- An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens.Genetics, selection, evolution : GSE · 2020Article
- STARD1 Functions in Mitochondrial Cholesterol Metabolism and Nascent HDL Formation. Gene Expression and Molecular mRNA Imaging Show Novel Splicing and a 1:1 Mitochondrial Association.Frontiers in endocrinology · 2020Review
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7 authors.
Funding
Abstract
In mammalian cells, active sodium transport and its derived functions (e.g., plasma membrane potential) are dictated by the activity of the Na(+),K(+)-ATPase (NK), whose regulation is essential for maintaining cell volume and composition, as well as other vital cell functions. Here we report the existence of a salt-inducible kinase-1 (SIK1) that associates constitutively with the NK regulatory complex and is responsible for increases in its catalytic activity following small elevations in intracellular sodium concentrations. Increases in intracellular sodium are paralleled by elevations in intracellular calcium through the reversible Na(+)/Ca(2+) exchanger, leading to the activation of SIK1 (Thr-322 phosphorylation) by a calcium calmodulin-dependent kinase. Activation of SIK1 results in the dephosphorylation of the NK alpha-subunit and an increase in its catalytic activity. A protein phosphatase 2A/phosphatase methylesterase-1 (PME-1) complex, which constitutively associates with the NK alpha-subunit, is activated by SIK1 through phosphorylation of PME-1 and its dissociation from the complex. These observations illustrate the existence of a distinct intracellular signaling network, with SIK1 at its core, which is triggered by a monovalent cation (Na(+)) and links sodium permeability to its active transport.
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