Drosophila terminal structure development is regulated by the compensatory activities of positive and negative phosphotyrosine signaling sites on the Torso RTK.
Specification of cell fates in the nonsegmented terminal regions of developing Drosophila embryos is under the 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-gammal, increases Tor signaling. Interestingly, when receptors contain mutations in both the Y630 and Y918 sites, Tor signaling is restored to wild-type levels. These results identify a novel mechanism whereby Tor function is regulated using compensatory signals generated from distinct autophosphorylation sites and reveal an underlying signaling pathway for terminal development.
Cleghon
V
V
National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA.
Gayko
U
U
Copeland
T D
TD
Perkins
L A
LA
Perrimon
N
N
Morrison
D K
DK
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D009154:Mutation; D010748:Phosphopeptides; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis; D017421:Sequence Analysis; D015398:Signal Transduction; D013379:Substrate Specificity; D014443:Tyrosine; D018909:src Homology Domains
D000596:Amino Acids; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C087725:Hkb protein, Drosophila; D010748:Phosphopeptides; D011994:Recombinant Proteins; D012097:Repressor Proteins; C074090:TLL protein, Drosophila; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases; C080148:tor protein, Drosophila; C098692:Csw protein, Drosophila; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor