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

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

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

Jungseog Kang,Yue Chen,Yingming Zhao,Hongtao Yu,Jungseog Kang,Yue Chen,Yingming Zhao,Hongtao Yu,

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.

Autophosphorylation-dependent activation of human Mps1 is required for the spindle checkpoint. Publishing Authors By Initials

J Kang,Y Chen,Y Zhao,H Yu,J Kang,Y Chen,Y Zhao,H Yu,

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 20232-7

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 14

MONTH: 12

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for Autophosphorylation-dependent activation of human Mps1 is required for the spindle checkpoint.

AFFILIATION: Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM61542

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

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