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PMID: 18083840 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Autophosphorylation-dependent activation of human Mps1 is required for the spindle checkpoint.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 51 ·2007-12-18 ·Pages 20232-7

Kang J, Chen Y, Zhao Y, Yu H

Abstract

The spindle checkpoint ensures the accuracy of chromosome segregation during mitosis. The protein serine/threonine kinase, Mps1, is a critical component of the spindle checkpoint in human cells and regulates the kinetochore localization of key checkpoint proteins. The kinase activity of Mps1 is required for the spindle checkpoint, but how Mps1 is activated during mitosis is unclear. Here, we show that the endogenous Mps1 in mitotic HeLa cells is phosphorylated on T676, a residue in the activation loop. This phosphorylation event on Mps1 is required for its kinase activity in vitro and for spindle checkpoint signaling in vivo. T676 phosphorylation of Mps1 increases during mitosis and can occur through intermolecular/trans autophosphorylation. Induced dimerization of Mps1 is sufficient to activate its kinase activity in cells. We speculate that the kinetochore localization of Mps1 raises its local concentration, leading to its activation during mitosis through more efficient trans autophosphorylation.

MeSH Terms
Amino Acid Sequence Cell Cycle Cell Cycle Proteins/analysis,genetics,metabolism Dimerization Enzyme Activation HeLa Cells Humans Kinetochores/chemistry Mitosis Molecular Sequence Data Phosphorylation Protein Conformation Protein Serine-Threonine Kinases/analysis,genetics,metabolism Protein-Tyrosine Kinases Spindle Apparatus/metabolism Tyrosine/metabolism
Chemicals
Cell Cycle Proteins Tyrosine Protein-Tyrosine Kinases Protein Serine-Threonine Kinases TTK protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kang Jungseog
Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
Chen Yue
Zhao Yingming
Yu Hongtao
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0710519105
Published
2007-12-18
Epub
2007-00-14
Pages
20232-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2154414
Subset
IM
Grants
NIGMS NIH HHS · R01 GM061542 · United States
NIGMS NIH HHS · GM61542 · United States
External Links
PubMed source DOI: 10.1073/pnas.0710519105 PMC Full Text View journal details
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