Multiple functions of raf proto-oncogene during development from analysis of a temperature-sensitive mutation of Drosophila.
A temperature-sensitive (ts) mutation of Drosophila melanogaster for D-raf, encoding a serine/threonine protein kinase, was newly induced by EMS-treatment. Temperature-shift experiments on the ts mutant revealed that D-raf is required during most of the developmental stages, and confirmed the previously reported roles of D-raf in the regulation of cell proliferation and in the determination of cell fates at terminal regions of the embryo (Nishida et al., EMBO J. 7:775-781, 1988; Ambrosio et al., Nature 342:288-291, 1989a). Detailed analysis of cell proliferation demonstrated the role of D-raf at other than M-phase in cell cycle. TSP analysis during pupal stages revealed yet another role of D-raf in eclosion. Mosaic analysis of an eclosion-defective hypomorphic mutation revealed the tissue responsible for this defect to be the muscle and/or nervous system in the thorax. Molecular lesion associated with the ts mutation was found to be an alteration of an amino acid residue in a highly conserved region that defines the kinase subdomain VIII. Molecular analysis of null mutations also suggested the importance of the kinase domain for the biological functions of D-raf. Elucidation of the multi-functional nature of signal transducers is of great importance for our understanding of the molecular mechanisms of development, and the ts mutation for pleiotropic D-raf obtained in this study promises to be useful for dissecting signal transduction pathways during development.
Hata
M
M
Laboratory of Experimental Radiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Inoue
Y H
YH
Yoo
M A
MA
Nishida
Y
Y
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000254:growth & development*; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D017344:Genes, Insect; D008297:Male; D009154:Mutation; D011519:Proto-Oncogenes; D015398:Signal Transduction; D013696:Temperature