ArticleBiochemistry2015
Domain-Swapping Switch Point in Ste20 Protein Kinase SPAK.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Kinase interaction analysis predicts actions of the WNK-OSR1/SPAK pathway.Communications biology · 2025Article
- Investigation of thiophene derivatives as potential antihypertensive agents: DFT, molecular docking and ADMET studies.In silico pharmacology · 2025Article
- Multi-tiered chemical proteomic maps of tryptoline acrylamide-protein interactions in cancer cells.Nature chemistry · 2024Article
- A critical evaluation of protein kinase regulation by activation loop autophosphorylation.eLife · 2023Article
- Crank up the volume: Osmotic stress induces WNK1 phase separation.Cell research · 2023Article
- CCT and CCT-Like Modular Protein Interaction Domains in WNK Signaling.Molecular pharmacology · 2022Review
- Structural and Functional Analyses of Human ChaC2 in Glutathione Metabolism.Biomolecules · 2019Article
- Structural Basis of Protein Kinase R Autophosphorylation.Biochemistry · 2019Article
- Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian Tubule.Journal of the American Society of Nephrology : JASN · 2018Article
- OSR1 regulates a subset of inward rectifier potassium channels via a binding motif variant.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Germinal-center kinase-like kinase co-crystal structure reveals a swapped activation loop and C-terminal extension.Protein science : a publication of the Protein Society · 2017Article
- WNK Kinases in Development and Disease.Current topics in developmental biology · 2017Review
- Oncogenic Mutations Differentially Affect Bax Monomer, Dimer, and Oligomeric Pore Formation in the Membrane.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The related protein kinases SPAK and OSR1 regulate ion homeostasis in part by phosphorylating cation cotransporter family members. The structure of the kinase domain of OSR1 was determined in the unphosphorylated inactive form and, like some other Ste20 kinases, exhibited a domain-swapped activation loop. To further probe the role of domain swapping in SPAK and OSR1, we have determined the crystal structures of SPAK 63-403 at 3.1 Å and SPAK 63-390 T243D at 2.5 Å resolution. These structures encompass the kinase domain and different portions of the C-terminal tail, the longer without and the shorter with an activating T243D point mutation. The structure of the T243D protein reveals significant conformational differences relative to unphosphorylated SPAK and OSR1 but also has some features of an inactive kinase. Both structures are domain-swapped dimers. Sequences involved in domain swapping were identified and mutated to create a SPAK monomeric mutant with kinase activity, indicating that monomeric forms are active. The monomeric mutant is activated by WNK1 but has reduced activity toward its substrate NKCC2, suggesting regulatory roles for domain swapping. The structure of partially active SPAK T243D is consistent with a multistage activation process in which phosphorylation induces a SPAK conformation that requires further remodeling to build the active structure.
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