The MPS1 family of protein kinases

Xuedong Liu, Mark Winey

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

MPS1 protein kinases are found widely, but not ubiquitously, in eukaryotes. This family of potentially dual-specific protein kinases is among several that regulate a number of steps of mitosis. The most widely conserved MPS1 kinase functions involve activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond mitosis, MPS1 kinases have been implicated in development, cytokinesis, and several different signaling pathways. Family members are identified by virtue of a conserved C-terminal kinase domain, though the N-terminal domain is quite divergent. The kinase domain of the human enzyme has been crystallized, revealing an unusual ATP-binding pocket. The activity, level, and subcellular localization of Mps1 family members are tightly regulated during cell-cycle progression. The mitotic functions of Mps1 kinases and their overexpression in some tumors have prompted the identification of Mps1 inhibitors and their active development as anticancer drugs.

Original languageEnglish (US)
Pages (from-to)561-585
Number of pages25
JournalAnnual Review of Biochemistry
Volume81
DOIs
StatePublished - Jul 1 2012
Externally publishedYes

Keywords

  • cell cycle
  • kinetochore
  • mitosis
  • spindle checkpoint
  • TTK

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry

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