The Doa locus encodes a member of a new protein kinase family and is essential for eye and embryonic development in Drosophila melanogaster.
Mutations at the Darkener of apricot (Doa) locus of Drosophila cause roughened eyes and increase transcript accumulation from the retrotransposon copia up to fourfold. Cloning of the gene and sequencing of cDNAs reveals that it encodes a putative serine/threonine protein kinase. Sequence data base searches identify it is a member of a novel highly conserved protein kinase family, with homologs in humans, mice, and Saccharomyces cerevisiae, not related to each other previously. Family members are characterized by a peptide motif reading EHLAMMERILG at kinase subdomain X, which is virtually 100% identical in all homologs. We therefore refer to this new family as the LAMMER protein kinases. As predicted from its primary sequence, Doa protein possess intrinsic protein kinase activity when expressed in bacteria, as assayed via autophosphorylation. The gene is expressed throughout development, and both stage and tissue-specific RNAs are found. Its function is essential, because maternally deposited or zygotically transcribed mRNA is required for development to larval stages, and defects in segmentation and development of the nervous system are observed in embryos derived from heteroallelic mothers. Doa function is also critical to Drosophila eye development, because the organization and development of pigment cells, bristles, and photoreceptors are affected in various mutant classes. In the most extreme cases that survive to adulthood, retinal photoreceptors degenerate prior to eclosion. These results demonstrate that the kinase encoded by Doa is required at multiple stages of development, for both differentiation and maintenance of specific cell types.
Yun
B
B
Waksman Institute, Rutgers University, Piscataway, New Jersey 08855-0759.
Farkas
R
R
Lee
K
K
Rabinow
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000254:growth & development; D005123:Eye / Q000254:growth & development / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D017344:Genes, Insect / Q000235:genetics*; D005804:Genes, Lethal; D005838:Genotype; D008297:Male; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D015183:Restriction Mapping; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D012333:RNA, Messenger; D011494:Protein Kinases; C089977:Doa protein, Drosophila; D017346:Protein Serine-Threonine Kinases