Evidence map›Paper›PMID 21712545›Full record

ArticleScience signaling2011

Spatial exclusivity combined with positive and negative selection of phosphorylation motifs is the basis for context-dependent mitotic signaling.

Jes Alexander, Daniel Lim, Brian A Joughin, Björn Hegemann, James R A Hutchins, Tobias Ehrenberger, Frank Ivins, Fabio Sessa, Otto Hudecz, Erich A Nigg and 7 more

Abstract read
In one paragraph

Article in Science signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.

0numbers the graph read from it
0cells of the map it votes in
119citing 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

119 citing papers in PubMed.

  1. Article
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  4. Decoding Cdk1 control: from mitotic thresholds to meiotic specificity.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2026
    Review
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  18. Marginal specificity in protein interactions constrains evolution of a paralogous family.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  19. Article
  20. Article

59 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

17 authors.

Jes AlexanderKoch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Daniel Lim
Brian A Joughin
Björn Hegemann
James R A Hutchins
Tobias Ehrenberger
Frank Ivins
Fabio Sessa
Otto Hudecz
Erich A Nigg
Andrew M Fry
Andrea Musacchio
P Todd Stukenberg
Karl Mechtler
Jan-Michael Peters
Stephen J Smerdon
Michael B Yaffe

Funding

Systems Biology of Cell Decision ProcessesP50GM068762 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 2003 to 2012
$32.3M
Tumor Cell Networks CenterU54CA112967 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LAUFFENBURGER, DOUGLAS A · 2004 to 2015
$26.2M
Protein Kinase Signaling and Cell Cycle ControlR01ES015339 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 2007 to 2017
$4.3M
PHOSPHOSERINE DEPENDENT ASSEMBLY OF SIGNALING COMPLEXESR01GM060594 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 2000 to 2007
$2.2M
Cancer Research UK A7820Cancer Research UK A9363Medical Research Council MC_U117584228NCI NIH HHS CA-112967NCI NIH HHS U54 CA112967NIEHS NIH HHS ES-015339NIEHS NIH HHS R01 ES015339NIGMS NIH HHS GM-60594NIGMS NIH HHS GM-68762NIGMS NIH HHS P50 GM068762NIGMS NIH HHS R01 GM060594Wellcome Trust 069035Wellcome Trust 078020Wellcome Trust 082828Worldwide Cancer Research 06-0029Worldwide Cancer Research 06-0407
6 · The paper itself

Abstract

The timing and localization of events during mitosis are controlled by the regulated phosphorylation of proteins by the mitotic kinases, which include Aurora A, Aurora B, Nek2 (never in mitosis kinase 2), Plk1 (Polo-like kinase 1), and the cyclin-dependent kinase complex Cdk1/cyclin B. Although mitotic kinases can have overlapping subcellular localizations, each kinase appears to phosphorylate its substrates on distinct sites. To gain insight into the relative importance of local sequence context in kinase selectivity, identify previously unknown substrates of these five mitotic kinases, and explore potential mechanisms for substrate discrimination, we determined the optimal substrate motifs of these major mitotic kinases by positional scanning oriented peptide library screening (PS-OPLS). We verified individual motifs with in vitro peptide kinetic studies and used structural modeling to rationalize the kinase-specific selection of key motif-determining residues at the molecular level. Cross comparisons among the phosphorylation site selectivity motifs of these kinases revealed an evolutionarily conserved mutual exclusion mechanism in which the positively and negatively selected portions of the phosphorylation motifs of mitotic kinases, together with their subcellular localizations, result in proper substrate targeting in a coordinated manner during mitosis.

Indexed as

Evolution, MolecularAmino Acid MotifsAnimalsHumansMitosisPeptide LibraryPhosphorylationProtein Serine-Threonine KinasesSignal TransductionXenopus laevisXenopus ProteinsPeptide LibraryProtein Serine-Threonine KinasesXenopus Proteins

Identifiers

PMID21712545
PMCPMC3939359

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.