The Mouse Mps1p-like Kinase Regulates Centrosome Duplication

Cell. 2001 Jul 13;106(1):95-104. doi: 10.1016/s0092-8674(01)00411-1.

Abstract

The yeast Mps1p protein kinase acts in centrosome duplication and the spindle assembly checkpoint. We demonstrate here that a mouse Mps1p ortholog (esk, which we designate mMps1p) regulates centrosome duplication. Endogenous mMps1p and overexpressed GFP-mMps1p localize to centrosomes and kinetochores in mouse cells. Overexpression of GFP-mMps1p causes reduplication of centrosomes during S phase arrest. In contrast, a kinase-deficient mutant blocks centrosome duplication altogether. Control of centrosome duplication by mMps1p requires a known regulator of the process, Cdk2. Inhibition of Cdk2 prevents centrosome reduplication and destabilizes mMps1p, causing its subsequent loss from centrosomes, suggesting that Cdk2 promotes mMps1p's centrosome duplication function by regulating its stability during S phase. Thus, mMps1p, an in vitro Cdk2 substrate, regulates centrosome duplication jointly with Cdk2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Substitution
  • Animals
  • Antigens / analysis
  • CDC2-CDC28 Kinases*
  • Cell Cycle / drug effects
  • Cell Cycle / physiology*
  • Cell Cycle Proteins*
  • Centrosome / physiology*
  • Centrosome / ultrastructure
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / metabolism
  • Cysteine Endopeptidases / metabolism
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Humans
  • Kinetochores / physiology
  • Kinetochores / ultrastructure
  • Luminescent Proteins / genetics
  • Mice
  • Microtubule-Associated Proteins / analysis
  • Mitosis
  • Multienzyme Complexes / metabolism
  • Mutagenesis, Site-Directed
  • Nocodazole / pharmacology
  • Proteasome Endopeptidase Complex
  • Protein Kinases*
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • S Phase
  • Telophase
  • Tetracycline / pharmacology
  • Transfection

Substances

  • Antigens
  • Cell Cycle Proteins
  • Luminescent Proteins
  • Microtubule-Associated Proteins
  • Multienzyme Complexes
  • Recombinant Fusion Proteins
  • pericentrin
  • Green Fluorescent Proteins
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cdk2 protein, mouse
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases
  • TTK protein, human
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Tetracycline
  • Nocodazole