Novel members of the cdc2-related kinase family in Drosophila: cdk4/6, cdk5, PFTAIRE, and PITSLRE kinase.
In addition to the previously identified Drosophila cdc2 and cdc2c genes, we have identified four additional cdc2-related genes with low stringency and polymerase chain reaction approaches. Sequence comparisons suggest that the four putative kinases represent the Drosophila homologues of vertebrate cdk4/6, cdk5, PCTAIRE, and PITSLRE kinases. Although the similarity between human and Drosophila homologues is extensive in the case of cdk5, PCTAIRE, and PITSLRE kinases (78%, 58%, and 65% identity in the kinase domain), only limited conservation is observed for Drosophila cdk4/6 (47% identity). However, like vertebrate cdk4 and cdk6, Drosophila cdk4/6 binds also to a D-type cyclin according to the results of two-hybrid experiments in yeast. Northern blot analysis indicated that the four Drosophila kinases are expressed throughout embryogenesis. Expression in early embryogenesis appeared to be ubiquitous according to in situ hybridization. Abundant expression already at the start of embryogenesis and long before neuron differentiation was also observed in the case of cdk5 protein, which has been described as predominantly neuron specific in mice. Sequence conservation and expression pattern, therefore, suggest that all of these kinases perform important cellular functions.
Sauer
K
K
Friedrich-Miescher-Laboratorium, Max-Planck-Gesellschaft, Tübingen, Germany.
Weigmann
K
K
Sigrist
S
S
Lehner
C F
CF
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D051358:Cyclin-Dependent Kinase 4; D051360:Cyclin-Dependent Kinase 5; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D018076:DNA, Complementary; D004330:Drosophila / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D015870:Gene Expression; D017344:Genes, Insect; D006657:Histones / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D018076:DNA, Complementary; D029721:Drosophila Proteins; D006657:Histones; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C447612:CDK11a protein, human; C495900:CDK4 protein, human; C495905:CDK5 protein, human; C495911:CDK6 protein, human; C495896:Cdk4 protein, Drosophila; C495904:Cdk5 protein, Drosophila; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases; C408322:Eip63E protein, Drosophila; C089463:PCTAIRE-1 protein kinase; C089464:PCTAIRE-3 protein kinase