The mouse Mps1p-like kinase regulates centrosome duplication.
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.
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MCD Biology, UCB 347, University of Colorado, Boulder, Boulder, CO 80309, USA.
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D016475:3T3 Cells; D019943:Amino Acid Substitution; D000818:Animals; D000941:Antigens / Q000032:analysis; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000502:physiology* / Q000648:ultrastructure; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D018386:Kinetochores / Q000502:physiology / Q000648:ultrastructure; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008938:Mitosis; D009097:Multienzyme Complexes / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D015739:Nocodazole / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016196:S Phase; D013692:Telophase; D013752:Tetracycline / Q000494:pharmacology; D014162:Transfection
D000941:Antigens; D018797:Cell Cycle Proteins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; C086178:pericentrin; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C075840:TTK protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D013752:Tetracycline; D015739:Nocodazole