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

Jungseog Kang, Yue Chen, Yingming Zhao, Hongtao Yu

Research output: Contribution to journalArticle

69 Scopus citations

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, buthow 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.

Original languageEnglish (US)
Pages (from-to)20232-20237
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number51
DOIs
StatePublished - Dec 18 2007

Keywords

  • Activation loop
  • Kinase
  • Kinetochore
  • Mitosis

ASJC Scopus subject areas

  • General

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