DEVELOPMENTAL AND MOLECULAR CHARACTERIZATION OF MUTATIONS IN THE DROSOPHILA-RAF SERINE THREONINE PROTEIN-KINASE

Formation of the tail region of the Drosophila larva requires the acti vities of the terminal class genes. Genetic and molecular analyses of these genes suggests that localized activation of the receptor tyrosin e kinase torso at the posterior egg pole triggers a signal transductio n pathway. This pathway, mediated through the serine/threonine protein kinase D-raf and the protein tyrosine phosphatase corkscrew, controls the domains of expression of the transcription factors tailless and h uckebein. In this paper, we report the molecular and developmental cha racterization of mutations in the D-raf gene. We show that mutations t hat alter conserved residues known to be necessary for kinase activity are associated with a null phenotype, demonstrating that D-raf kinase activity is required for its role in torso signaling. Another mutatio n, D-raf(PB26), which prematurely truncates the kinase domain shows a weaker maternal effect phenotype that is strikingly similar to the cor kscrew maternal effect phenotype, suggesting that a lower amount of ki nase activity decreases the terminal signaling pathway. Finally, molec ular and developmental characterization of two mutations that affect t he late D-raf zygotic function(s) implies a novel role for D-raf in ce ll fate establishment in the eve. One of these mutations, D-raf(C110), is associated with a single amino acid change within the putative D-r af regulatory region, while the other, D-raf(HM-7), most likely reduce s the wild-type amount of D-raf protein.