ArticleProceedings of the National Academy of Sciences of the United States of America2002
Identification of phosphorylated residues that affect the activity of the mitotic kinase Aurora-A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed.
- Molecular basis for the activation of Aurora A and Plk1 kinases during mitotic entry.The EMBO journal · 2026Article
- Molecular requirements for PLK1 activation by T-loop phosphorylation.The EMBO journal · 2026Article
- Splice-switching ASOs targeting the AURKA 5' UTR collapse an SRSF1-AURKA-MYC oncogenic circuit in pancreatic cancer.Molecular cell · 2026Article
- Aurora A regulates the material property of spindle poles to orchestrate nuclear organization at mitotic exit.The EMBO journal · 2025Article
- Chromatin-associated α-satellite RNA maintains chromosome stability by reestablishing SAF-A in the mitotic cell cycle.Nucleic acids research · 2025Article
- A novel role of AURKA kinase in erythroblast enucleation.Haematologica · 2024Article
- Article
- The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer.Cell proliferation · 2024Review
- Article
- Preclinical Evaluation of JAB-2485, a Potent AURKA Inhibitor with High Selectivity and Favorable Pharmacokinetic Properties.ACS omega · 2024Article
- vNARs as Neutralizing Intracellular Therapeutic Agents: Glioblastoma as a Target.Antibodies (Basel, Switzerland) · 2024Review
- Deletion of Aurora kinase A prevents the development of polycystic kidney disease in mice.Nature communications · 2024Article
- Aurora Kinase A: Integrating Insights into Cancer, Inflammation, and Infectious Diseases.Gut microbes reports · 2024Review
- Emerging roles of Aurora-A kinase in cancer therapy resistance.Acta pharmaceutica Sinica. B · 2023Review
- Structural basis for CEP192-mediated regulation of centrosomal AURKA.Science advances · 2023Article
- Revisiting degron motifs in human AURKA required for its targeting by APC/CLife science alliance · 2023Article
- CHD1, a multifaceted epigenetic remodeler in prostate cancer.Frontiers in oncology · 2023Review
- Primary Cilia Restrain PI3K-AKT Signaling to Orchestrate Human Decidualization.International journal of molecular sciences · 2022Article
- CHD1 Promotes Sensitivity to Aurora Kinase Inhibitors by Suppressing Interaction of AURKA with Its Coactivator TPX2.Cancer research · 2022Article
- Screening for Inhibitors of YAP Nuclear Localization Identifies Aurora Kinase A as a Modulator of Lung Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activity of the kinase Aurora-A (Aur-A) peaks during mitosis and depends on phosphorylation by one or more unknown kinases. Mitotic phosphorylation sites were mapped by mass spec sequencing of recombinant Aur-A protein that had been activated by incubation in extracts of metaphase-arrested Xenopus eggs. Three sites were identified: serine 53 (Ser-53), threonine 295 (Thr-295), and serine 349 (Ser-349), which are equivalent to Ser-51, Thr-288, and Ser-342, respectively, in human Aur-A. To ask how phosphorylation of these residues might affect kinase activity, each was mutated to either alanine or aspartic acid, and the recombinant proteins were then tested for their ability to be activated by M phase extract. Mutation of Thr-295, which resides in the activation loop of the kinase, to either alanine or aspartic acid abolished activity. The S349A mutant had slightly reduced activity, indicating that phosphorylation is not required for activity. The S349D mutation completely blocked activation, suggesting that Ser-349 is important for either the structure or regulation of Aur-A. Finally, like human Aur-A, overexpression of Xenopus Aur-A transformed NIH 3T3 cells and led to tumors in nude mice. These results provide further evidence that Xenopus Aur-A is a functional ortholog of human Aur-A and, along with the recently described crystal structure of human Aur-A, should help in future studies of the mechanisms that regulate Aur-A activity during mitotic progression.
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