Specification of cell fates in the nonsegmented terminal regions of developing Drosophila embryos is underthe control of a signal transduction pathway mediated by the receptor tyrosine kinase Torso (Tor). Here, we identify tyrosines (Y) 630 and 918 as the major sites of Tor autophosphorylation. We demonstrate that mutation of Y630, a site required for association with and tyrosine phosphorylation of the tyrosine phosphatase Corkscrew, decreases the efficiency of Tor signaling. In contrast, mutation of Y918, a site capable of binding mammalian rasGAP and PLC-3,1, increases Tor signaling. Interestingly, when receptors contain mutations in both the Y630 and Y918 sites, Tot signaling is restored to wild-type levels. These results identify a novel mechanism whereby Tot function is regulated using compensatory signals generated from distinct autophosphorylation sites and reveal an underlying signaling pathway for terminal development.[Key Words: Receptor tyrosine kinase; Drosophila; Torso; Corkscrew] Received December 13, 1995; revised version accepted January 25, 1996.The formation of multicellular organisms requires the orchestrated transmission, reception, and propagation of temporal and spatial developmental signals. Many of these signaling events are transduced by proteins of the receptor tyrosine kinase (RTK) family. RTKs function in developmental, mitogenic, and oncogenic signal transduction pathways and in organisms as diverse as mammals, Drosophila melanogaster, and Caenorhabditis elegans (Pawson and Berbstein 1990;Lu et al. 1993b). For many RTKs, binding of the cognate ligand leads to receptor dimerization followed by auto-or transphosphorylation on tyrosine residues (Heldin 1995). This phosphorylation event creates specific docking sites for a variety of cytosolic molecules, such as Src homology 2 (SH2) domain-containing proteins (Cantley et al. 1991;Koch et al. 1991;Cohen et al. 1995) and phosphotyrosine binding (PTB) domain-containing proteins (Blaikie et al. 1994;Kavanaugh and Williams 1994). Determining the significance and function of receptor-binding events is a key issue in understanding how RTKs transduce such a diverse array of signals. Most studies have addressed this problem by mutating individual RTK phosphorylation (and docking) sites and then assessing the consequences of these mutations on receptor function. Although this 4Corresponding author. approach has provided many insights into the molecular mechanisms of RTK-mediated signaling, most of the biological assays employed are based on tissue culture systems rather than on intact organisms in which the RTK actually functions.Early Drosophila embryogenesis, and in particular, activation of the Torso (Tor) RTK pathway, provides an attractive in vivo model system with which to study the genetic and molecular mechanisms of RTK signal transduction (for review, see Lu et al. 1993b; Duffy and Perrimon, 1994). In the developing Drosophila embryo, activation of the Tot RTK leads to the formation of specialized anterior and posterior terminal structu...