ArticleNature communications2015
Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer.Nature communications · 2026Article
- NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3.Scientific reports · 2026Article
- NEKfla: A Genetically Encoded Förster Resonance Energy Transfer Biosensor for Live-Cell Monitoring of Early NIMA-Related Kinase 7-NLR Family Pyrin Domain Containing 3 Inflammasome Signaling.Biomaterials research · 2026Article
- Discriminating activating, deactivating and resistance variants in protein kinases.Genome medicine · 2025Article
- NEK Family Kinases: Structure, Function, and Role in Disease.Biomolecules · 2025Review
- NEK kinases in cell cycle regulation, DNA damage response, and cancer progression.Tissue & cell · 2025Review
- Article
- AS160 is a lipid-responsive regulator of cardiac CaNature communications · 2024Article
- Genetically evaluating the causal role of peripheral immune cells in colorectal cancer: a two-sample Mendelian randomization study.BMC cancer · 2024Article
- Synthesis, biological evaluation andRSC advances · 2023Article
- Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation.Annual review of immunology · 2023Review
- Identification of biological pathways and processes regulated by NEK5 in breast epithelial cells via an integrated proteomic approach.Cell communication and signaling : CCS · 2022Article
- Deep Learning and Structure-Based Virtual Screening for Drug Discovery against NEK7: A Novel Target for the Treatment of Cancer.Molecules (Basel, Switzerland) · 2022Article
- A Single Amino Acid Residue Defines the Difference in NLRP3 Inflammasome Activation between NEK7 and NEK6.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022Review
- Analysis of the effect of NEKs on the prognosis of patients with non-small-cell lung carcinoma based on bioinformatics.Scientific reports · 2022Article
- Activation and regulation mechanisms of NOD-like receptors based on structural biology.Frontiers in immunology · 2022Review
- An RRx-001 Analogue With Potent Anti-NLRP3 Inflammasome Activity but Without High-Energy Nitro Functional Groups.Frontiers in pharmacology · 2022Article
- Inhibition of the NLRP3 Inflammasome Activation by Manoalide Ameliorates Experimental Autoimmune Encephalomyelitis Pathogenesis.Frontiers in cell and developmental biology · 2022Article
- RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor.Cellular & molecular immunology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Mitotic spindle assembly requires the regulated activities of protein kinases such as Nek7 and Nek9. Nek7 is autoinhibited by the protrusion of Tyr97 into the active site and activated by the Nek9 non-catalytic C-terminal domain (CTD). CTD binding apparently releases autoinhibition because mutation of Tyr97 to phenylalanine increases Nek7 activity independently of Nek9. Here we find that self-association of the Nek9-CTD is needed for Nek7 activation. We map the minimal Nek7 binding region of Nek9 to residues 810-828. A crystal structure of Nek7(Y97F) bound to Nek9(810-828) reveals a binding site on the C-lobe of the Nek7 kinase domain. Nek7(Y97F) crystallizes as a back-to-back dimer between kinase domain N-lobes, in which the specific contacts within the interface are coupled to the conformation of residue 97. Hence, we propose that the Nek9-CTD activates Nek7 through promoting back-to-back dimerization that releases the autoinhibitory tyrosine residue, a mechanism conserved in unrelated kinase families.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.