ArticleThe Journal of biological chemistry2009
Discovery and exploitation of inhibitor-resistant aurora and polo kinase mutants for the analysis of mitotic networks.
Article in The Journal of biological chemistry, 2009. 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.
- Exploring the Conformational Landscape and Stability of Aurora A Using Ion-Mobility Mass Spectrometry and Molecular Modeling.Journal of the American Society for Mass Spectrometry · 2022Article
- Reversing tozasertib resistance in glioma through inhibition of pyruvate dehydrogenase kinases.Molecular oncology · 2022Article
- Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC).Breast cancer (Tokyo, Japan) · 2021Article
- Use of the Polo-like kinase 4 (PLK4) inhibitor centrinone to investigate intracellular signalling networks using SILAC-based phosphoproteomics.The Biochemical journal · 2020Article
- Covalent Aurora A regulation by the metabolic integrator coenzyme A.Redox biology · 2020Article
- Overcome cancer drug resistance by targeting epigenetic modifications of centrosome.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells.Science signaling · 2018Article
- New tools for carbohydrate sulfation analysis: heparan sulfate 2-The Biochemical journal · 2018Article
- New tools for evaluating protein tyrosine sulfation: tyrosylprotein sulfotransferases (TPSTs) are novel targets for RAF protein kinase inhibitors.The Biochemical journal · 2018Article
- Global assessment of its network dynamics reveals that the kinase Plk1 inhibits the phosphatase PP6 to promote Aurora A activity.Science signaling · 2018Article
- Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes.The Journal of cell biology · 2017Article
- KinView: a visual comparative sequence analysis tool for integrated kinome research.Molecular bioSystems · 2016Article
- 'Up with the LRRK': a phosphorylated Rab10 assay for evaluation of LRRK2 activity and inhibitor engagement.The Biochemical journal · 2016Article
- A FRET biosensor reveals spatiotemporal activation and functions of aurora kinase A in living cells.Nature communications · 2016Article
- Article
- Hydrophobic Core Variations Provide a Structural Framework for Tyrosine Kinase Evolution and Functional Specialization.PLoS genetics · 2016Article
- PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase.Scientific reports · 2015Article
- Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis.Molecular and cellular biology · 2015Article
- The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates in a metal-independent manner.The Biochemical journal · 2015Article
- Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The Aurora and Polo-like kinases are central components of mitotic signaling pathways, and recent evidence suggests that substantial cross-talk exists between Aurora A and Plk1. In addition to their validation as novel anticancer agents, small molecule kinase inhibitors are increasingly important tools to help dissect clinically relevant protein phosphorylation networks. However, one major problem associated with kinase inhibitors is their promiscuity toward "off-target" members of the kinome, which makes interpretation of data obtained from complex cellular systems challenging. Additionally, the emergence of inhibitor resistance in patients makes it clear that an understanding of resistance mechanisms is essential to inform drug design. In this study, we exploited structural knowledge of the binding modes of VX-680, an Aurora kinase inhibitor, and BI 2536, a Polo-like kinase inhibitor, to design and evaluate drug-resistant kinase mutants. Using inducible stable human cell lines, we authenticated mitotic targets for both compounds and demonstrated that Aurora A mutants exhibit differential cellular sensitivity toward the inhibitors VX-680 and MLN8054. In addition, we validated Aurora B as an important anti-proliferative target for VX-680 in model human cancer cells. Finally, this chemical genetic approach allowed us to prove that Aurora A activation loop phosphorylation is controlled by a Plk1-mediated pathway in human cells.
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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.