Synergistic activities of multiple phosphotyrosine residues mediate full signaling from the Drosophila Torso receptor tyrosine kinase

Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):523-8. doi: 10.1073/pnas.96.2.523.


Here, we identify four tyrosine residues (Y644, Y698, Y767, and Y772) that become phosphorylated after activation of the Torso (Tor) receptor tyrosine kinase. Previously, we characterized phosphotyrosine sites (P-Y630 and P-Y918). Of the six P-Y sites identified, three (Y630, Y644, and Y698) are located in the kinase domain insert region, one (Y918) is located in the C-terminal tail region, and two (Y767 and Y772) are located in the activation loop of the kinase domain. To investigate the function of each P-Y residue in Tor signaling, we have generated transgenic Drosophila embryos expressing mutant Tor receptors containing either single or multiple tyrosine to phenylalanine substitutions. Single P-Y mutations were found to have either positive, negative, or no effect on the signaling activity of the receptor. Elimination of all P-Y sites within the kinase insert region resulted in the complete loss of receptor function, indicating that some combination of these sites is necessary for Tor signaling. Mutation of the C-terminal P-Y918 site revealed that this site is responsible for negative signaling or down-regulation of receptor activity. Mutation of the P-Y sites in the kinase domain activation loop demonstrated that these sites are essential for enzymatic activity. Our analysis provides a detailed in vivo example of the extent of cooperativity between P-Y residues in transducing the signal received by a receptor tyrosine kinase and in vivo data demonstrating the function of P-Y residues in the activation loop of the kinase domain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila / embryology
  • Drosophila / genetics*
  • Drosophila Proteins*
  • Embryonic Development
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Mutation / genetics
  • Phosphopeptides / analysis
  • Phosphorylation
  • Phosphotyrosine / genetics
  • Phosphotyrosine / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Recombinant Proteins / genetics
  • Signal Transduction / genetics
  • Structure-Activity Relationship


  • Drosophila Proteins
  • Insect Proteins
  • Phosphopeptides
  • Recombinant Proteins
  • Phosphotyrosine
  • Receptor Protein-Tyrosine Kinases
  • tor protein, Drosophila