DISSECTION OF THE TORSO SIGNAL-TRANSDUCTION PATHWAY IN DROSOPHILA

Cell fate choice at the anterior and posterior embryonic termini of th e Drosophila embryo requires the activation of a signal transduction p athway regulated by the receptor tyrosine kinase Torso. When Torso, wh ich is uniformly distributed in the egg cell membrane, becomes activat ed locally at the termini, it triggers a phosphorylation cascade that culminates with localized expression of the transcription factors, tai lless and huckebein. Expression of tailless and huckebein in turn dete rmines terminal cell fates. Several genes have been characterized whic h encode proteins that are involved in Torso signaling: the adaptor pr otein Drk, the GTP-binding protein Ras1, the guanine nucleotide exchan ge factor Son of sevenless, and the kinases D-Raf and D-Mek Genetic an d molecular evidence supports a model in which these proteins lie in t he same biochemical pathway. When activated by its ligand the membrane -bound receptor tyrosine kinase Torso initiates a signal transduction pathway mediated by Drk, Sos, and Ras1, which in turn activates a phos phorylation cascade mediated by the kinases D-Raf and D-Mek, which ult imately control the localized expression of the transcription factors tailless and huckebein. Recently, we found that D-Raf can be partially activated by Torso in the absence of Ras1, a finding supported by the phenotype of embryos lacking either Drk or Sos activity, as well as b y the phenotype of a D-raf mutation that abolishes binding of Ras1 to D-Raf. These findings indicate that full D-Raf activation requires inp ut not only from Ras1 but also from an as yet uncharacterized Ras1-ind ependent pathway. In addition to these molecules we have characterized the putative protein tyrosine phosphatase Corkscrew as a positive tra nsducer downstream of Torso. (C) 1995 Wiley-Liss, Inc.