title: A screen for modifiers of cyclin E function in Drosophila melanogaster identifies Cdk2 mutations, revealing the insignificance of putative phosphorylation sites in Cdk2.
abstract: In higher eukaryotes, cyclin E is thought to control the progression from G1 into S phase of the cell cycle by associating as a regulatory subunit with cdk2. To identify genes interacting with cyclin E, we have screened in Drosophila melanogaster for mutations that act as dominant modifiers of an eye phenotype caused by a Sevenless-CycE transgene that directs ectopic Cyclin E expression in postmitotic cells of eye imaginal disc and causes a rough eye phenotype in adult flies. The majority of the EMS-induced mutations that we have identified fall into four complementation groups corresponding to the genes split ends, dacapo, dE2F1, and Cdk2(Cdc2c). The Cdk2 mutations in combination with mutant Cdk2 transgenes have allowed us to address the regulatory significance of potential phosphorylation sites in Cdk2 (Thr 18 and Tyr 19). The corresponding sites in the closely related Cdk1 (Thr 14 and Tyr 15) are of crucial importance for regulation of the G2/M transition by myt1 and wee1 kinases and cdc25 phosphatases. In contrast, our results demonstrate that the equivalent sites in Cdk2 play no essential role.
authors.affiliation: Department of Genetics, University of Bayreuth, 95440 Bayreuth, Germany.
authors.forename: M E
authors.initials: ME
authors.lastname: Lane
authors.forename: M
authors.initials: M
authors.lastname: Elend
authors.forename: D
authors.initials: D
authors.lastname: Heidmann
authors.forename: A
authors.initials: A
authors.lastname: Herr
authors.forename: S
authors.initials: S
authors.lastname: Marzodko
authors.forename: A
authors.initials: A
authors.lastname: Herzig
authors.forename: C F
authors.initials: CF
authors.lastname: Lehner
mesh_terms: D000818:Animals; D001665:Binding Sites; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D050684:E2F Transcription Factors; D004742:Enhancer Elements, Genetic; D005123:Eye; D005136:Eye Proteins / Q000235:genetics; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics; D007814:Larva / Q000254:growth & development; D008562:Membrane Glycoproteins / Q000235:genetics; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D020794:Receptor Protein-Tyrosine Kinases; D056465:Retinoblastoma-Binding Protein 1; D013912:Threonine / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D014443:Tyrosine / Q000235:genetics; D015053:Zygote
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D005136:Eye Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D056465:Retinoblastoma-Binding Protein 1; C402387:Spen protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; C103336:dap protein, Drosophila; D013912:Threonine; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C495887:cdk2 protein, Drosophila