Opposing actions of CSW and RasGAP modulate the strength of Torso RTK signaling in the Drosophila terminal pathway.
In Drosophila, specification of embryonic terminal cells is controlled by the Torso receptor tyrosine kinase. Here, we analyze the molecular basis of positive (Y630) and negative (Y918) phosphotyrosine (pY) signaling sites on Torso. We find that the Drosophila homolog of RasGAP associates with pY918 and is a negative effector of Torso signaling. Further, we show that the tyrosine phosphatase Corkscrew (CSW), which associates with pY630, specifically dephosphorylates the negative pY918 Torso signaling site, thus identifying Torso to be a substrate of CSW in the terminal pathway. CSW also serves as an adaptor protein for DRK binding, physically linking Torso to Ras activation. The opposing actions of CSW and RasGAP modulate the strength of the Torso signal, contributing to the establishment of precise boundaries for terminal structure development.
Cleghon
V
V
Molecular Basis of Carcinogenesis Laboratory, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA.
Feldmann
P
P
Ghiglione
C
C
Copeland
T D
TD
Perrimon
N
N
Hughes
D A
DA
Morrison
D K
DK
D000818:Animals; D001665:Binding Sites; D004330:Drosophila / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins; D019476:Insect Proteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D029721:Drosophila Proteins; D019476:Insect Proteins; D011506:Proteins; C491146:RasGAP1 protein, Drosophila; D012097:Repressor Proteins; C080530:drk protein, Drosophila; D020703:ras GTPase-Activating Proteins; D019000:Phosphotyrosine; 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