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PMID: 18923149 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Regulation of kinetochore recruitment of two essential mitotic spindle checkpoint proteins by Mps1 phosphorylation.

Molecular biology of the cell ·Vol. 20 ·No. 1 ·2009-01-00 ·Pages 10-20

Xu Q, Zhu S, Wang W, Zhang X, Old W, Ahn N, Liu X

Abstract

Mps1 is a protein kinase that plays essential roles in spindle checkpoint signaling. Unattached kinetochores or lack of tension triggers recruitment of several key spindle checkpoint proteins to the kinetochore, which delays anaphase onset until proper attachment or tension is reestablished. Mps1 acts upstream in the spindle checkpoint signaling cascade, and kinetochore targeting of Mps1 is required for subsequent recruitment of Mad1 and Mad2 to the kinetochore. The mechanisms that govern recruitment of Mps1 or other checkpoint proteins to the kinetochore upon spindle checkpoint activation are incompletely understood. Here, we demonstrate that phosphorylation of Mps1 at T12 and S15 is required for Mps1 recruitment to the kinetochore. Mps1 kinetochore recruitment requires its kinase activity and autophosphorylation at T12 and S15. Mutation of T12 and S15 severely impairs its kinetochore association and markedly reduces recruitment of Mad2 to the kinetochore. Our studies underscore the importance of Mps1 autophosphorylation in kinetochore targeting and spindle checkpoint signaling.

MeSH Terms
Amino Acid Sequence Animals Calcium-Binding Proteins/genetics,metabolism Cell Cycle Proteins/genetics,metabolism Cell Line Humans Kinetochores/metabolism Mad2 Proteins Molecular Sequence Data Phosphorylation Protein Serine-Threonine Kinases/genetics,metabolism Protein-Tyrosine Kinases RNA, Small Interfering/metabolism Recombinant Fusion Proteins/genetics,metabolism Repressor Proteins/genetics,metabolism Signal Transduction/physiology Spindle Apparatus/metabolism
Chemicals
Calcium-Binding Proteins Cell Cycle Proteins MAD2L1 protein, human Mad2 Proteins RNA, Small Interfering Recombinant Fusion Proteins Repressor Proteins Protein-Tyrosine Kinases Protein Serine-Threonine Kinases TTK protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Xu Quanbin
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
Zhu Songcheng
Wang Wei
Zhang Xiaojuan
Old William
Ahn Natalie
Liu Xuedong
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e08-03-0324
Published
2009-01-00
Epub
2008-00-15
Pages
10-20
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2613107
Subset
IM
Grants
NCI NIH HHS · R01 CA107098 · United States
NCI NIH HHS · R01 CA107098-05A1 · United States
NCI NIH HHS · CA-107098 · United States
External Links
PubMed source DOI: 10.1091/mbc.e08-03-0324 PMC Full Text View journal details
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