Evidence map›Paper›PMID 12422018›Full record

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.

Laurie E Littlepage, Hua Wu, Thorkell Andresson, Julia K Deanehan, Laufey T Amundadottir, Joan V Ruderman

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

103 citing papers in PubMed.

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43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Laurie E LittlepageDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Hua Wu
Thorkell Andresson
Julia K Deanehan
Laufey T Amundadottir
Joan V Ruderman

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Protein Processing, Post-TranslationalUbiquitin-Protein Ligase Complexes3T3 CellsAmino Acid SequenceAmino Acid SubstitutionAnaphase-Promoting Complex-CyclosomeAnimalsAurora Kinase AAurora KinasesCell Cycle ProteinsCell Transformation, NeoplasticEgg ProteinsEnzyme ActivationEnzyme InhibitorsFemaleGene Expression Regulation, NeoplasticAnaphase-Promoting Complex-CyclosomeAurka protein, mouseAURKA protein, XenopusAurora Kinase AAurora KinasesCell Cycle ProteinsEgg ProteinsEnzyme InhibitorsLigasesPhosphoprotein PhosphatasesPhosphoserinePhosphothreonineProtein Kinase InhibitorsProtein KinasesProtein Serine-Threonine KinasesProto-Oncogene ProteinsRecombinant Fusion ProteinsUbiquitinUbiquitin-Protein Ligase ComplexesXenopus Proteins

Identifiers

PMID12422018
PMCPMC137735

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Registered trials

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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.