ArticleMolecular and cellular biology2006
Characterization of SPAK and OSR1, regulatory kinases of the Na-K-2Cl cotransporter.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87 citing papers in PubMed, 164 citations in OpenAlex.
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- Multiple molecular mechanisms are involved in the activation of the kidney sodium-chloride cotransporter by hypokalemia.Kidney international · 2022Article
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- Hydrocephalus: historical analysis and considerations for treatment.European journal of medical research · 2022Review
- Regulation of the p38-MAPK pathway by hyperosmolarity and by WNK kinases.Scientific reports · 2022Article
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- The Different Temozolomide Effects on Tumorigenesis Mechanisms of Pediatric Glioblastoma PBT24 and SF8628 Cell Tumor in CAM Model and on Cells In Vitro.International journal of molecular sciences · 2022Article
- NKCC1 and KCC2: Structural insights into phospho-regulation.Frontiers in molecular neuroscience · 2022Review
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- Effect of Media with Different Glycerol Concentrations on Sheep Red Blood Cells' Viability In Vitro.Animals : an open access journal from MDPI · 2021Article
- WNKs are potassium-sensitive kinases.American journal of physiology. Cell physiology · 2021Article
- Advances in the development of novel compounds targeting cation-chloride cotransporter physiology.American journal of physiology. Cell physiology · 2021Review
- WNK4 kinase: from structure to physiology.American journal of physiology. Renal physiology · 2021Review
- STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway.Theranostics · 2021Article
27 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
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Abstract
Our recent studies demonstrate that SPAK (Ste20p-related Proline Alanine-rich Kinase), in combination with WNK4 [With No lysine (K) kinase], phosphorylates and stimulates the Na-K-2Cl cotransporter (NKCC1), whereas catalytically inactive SPAK (K104R) fails to activate the cotransporter. The catalytic domain of SPAK contains an activation loop between the well-conserved DFG and APE motifs. We speculated that four threonine residues (T231, T236, T243, and T247) in the activation loop might be sites of phosphorylation and kinase activation; therefore, we mutated each residue into an alanine. In this report, we demonstrate that coexpression of SPAK (T243A) or SPAK (T247A) with WNK4 not only prevented, but robustly inhibited, cotransporter activity in NKCC1-injected Xenopus laevis oocytes. These activation loop mutations produced an effect similar to that of the SPAK (K104R) mutant. In vitro phosphorylation experiments demonstrate that both intramolecular autophosphorylation of SPAK and phosphorylation of NKCC1 are significantly stronger in the presence of Mn2+ rather than Mg2+. We also show that SPAK activity is markedly inhibited by staurosporine and K252a, partially inhibited by N-ethylmaleimide and diamide, and unaffected by arsenite. OSR1, a kinase closely related to SPAK, exhibited similar kinase properties and similar functional activation of NKCC1 when coexpressed with WNK4.
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