MULTIPLE FUNCTIONS OF RAF PROTOONCOGENE DURING DEVELOPMENT FROM ANALYSIS OF A TEMPERATURE-SENSITIVE MUTATION OF DROSOPHILA

作者：HATA M; INOUE YH; YOO MA; NISHIDA Y

来源：International Journal of Developmental Biology, 1994, 38(2): 329-335.

• PROLIFERATION
• SIGNAL TRANSDUCTION
• TERMINAL SYSTEM
• MOLECULAR LESION

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.

• 出版日期1994-6