@article {843301,
	title = {Synergistic activities of multiple phosphotyrosine residues mediate full signaling from the Drosophila Torso receptor tyrosine kinase.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {96},
	number = {2},
	year = {1999},
	month = {1999 Jan 19},
	pages = {523-8},
	abstract = {
	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.

},
	keywords = {Animals, Animals, Genetically Modified, Drosophila, Drosophila Proteins, Embryonic Development, Insect Proteins, Mutation, Phosphopeptides, Phosphorylation, Phosphotyrosine, Receptor Protein-Tyrosine Kinases, Recombinant Proteins, Signal Transduction, Structure-Activity Relationship},
	issn = {0027-8424},
	author = {Gayko, U and Cleghon, V and Copeland, T and Morrison, D K and Perrimon, N}
}
