Evidence map›Paper›PMID 19120698›Full record

ArticleJournal of cellular and molecular medicine2009

Structural and mechanistic insights into Mps1 kinase activation.

Wei Wang, Yuting Yang, Yuefeng Gao, Quanbin Xu, Feng Wang, Songcheng Zhu, William Old, Katheryn Resing, Natalie Ahn, Ming Lei and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.9field-weighted citation impact, top 28% of its field
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

21 citing papers in PubMed, 46 citations in OpenAlex.

  1. MPS1 inhibition as an anticancer strategy: where do we stand?Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Mechanisms of Mitotic Kinase Regulation: A Structural Perspective.Frontiers in cell and developmental biology · 2018
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. The MPS1 family of protein kinases.Annual review of biochemistry · 2012
    Review
  18. Article
  19. Article
  20. Article
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

11 authors at 3 institutions in 1 country.

Wei WangDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
Yuting YangDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Yuefeng GaoDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
Quanbin XuDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
Feng WangDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Songcheng ZhuDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
William OldDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
Katheryn ResingDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
Natalie AhnDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
Ming LeiDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Xuedong LiuDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
University of Colorado Boulder · USUniversity of Michigan · USHoward Hughes Medical Institute · US

Funding

Mechanisms of p27Kipl Proteolysis in Cancer CellsR01CA107098 · NCI · UNIVERSITY OF COLORADO AT BOULDER · PI LIU, XUEDONG · 2004 to 2012
$2.7M
NCI NIH HHS CA107098NCI NIH HHS R01 CA107098NCI NIH HHS Y1-CO-1020NIGMS NIH HHS Y1-GM-1104
6 · The paper itself

Abstract

Mps1 is one of the several essential kinases whose activation is required for robust mitotic spindle checkpoint signalling. The activity of Mps1 is tightly regulated and increases dramatically during mitosis or in response to spindle damage. To understand the molecular mechanism underlying Mps1 regulation, we determined the crystal structure of the kinase domain of Mps1. The 2.7-A-resolution crystal structure shows that the Mps1 kinase domain adopts a unique inactive conformation. Intramolecular interactions between the key Glu residue in the C helix of the N-terminal lobe and the backbone amides in the catalytic loop lock the kinase in the inactive conformation. Autophosphorylation appears to be a priming event for kinase activation. We identified Mps1 autophosphorylation sites in the activation and the P+1 loops. Whereas activation loop autophosphorylation enhances kinase activity, autophosphorylation at the P+1 loop (T686) is associated with the active kinase. Mutation of T686 autophosphorylation site impairs both autophosphorylation and transphosphorylation. Furthermore, we demonstrated that phosphorylation of T676 may be a priming event for phosphorylation at T686. Finally, we identified two critical lysine residues in the loop between helices EF and F that are essential for substrate recruitment and maintaining high levels of kinase activity. Our studies reveal critical biochemical mechanisms for Mps1 kinase regulation.

Indexed as

Amino Acid SequenceCell Cycle ProteinsEnzyme ActivationHumansModels, MolecularMolecular Sequence DataMutationPhosphorylationProtein ConformationProtein Serine-Threonine KinasesProtein-Tyrosine KinasesSubstrate SpecificityCell Cycle ProteinsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesTTK protein, human

Identifiers

PMID19120698
PMCPMC2829362
OpenAlexW2022818656

What OpenQuestion holds

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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.