Analysis of corkscrew signaling in the Drosophila epidermal growth factor receptor pathway during myogenesis.
The Drosophila nonreceptor protein tyrosine phosphatase, Corkscrew (Csw), functions positively in multiple receptor tyrosine kinase (RTK) pathways, including signaling by the epidermal growth factor receptor (EGFR). Detailed phenotypic analyses of csw mutations have revealed that Csw activity is required in many of the same developmental processes that require EGFR function. However, it is still unclear where in the signaling hierarchy Csw functions relative to other proteins whose activities are also required downstream of the receptor. To address this issue, genetic interaction experiments were performed to place csw gene activity relative to the EGFR, spitz (spi), rhomboid (rho), daughter of sevenless (DOS), kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin. We followed the EGFR-dependent formation of VA2 muscle precursor cells as a sensitive assay for these genetic interaction studies. First, we established that Csw has a positive function during mesoderm development. Second, we found that tissue-specific expression of a gain-of-function csw construct rescues loss-of-function mutations in other positive signaling genes upstream of rolled (rl)/MAPK in the EGFR pathway. Third, we were able to infer levels of EGFR signaling in various mutant backgrounds during myogenesis. This work extends previous studies of Csw during Torso and Sevenless RTK signaling to include an in-depth analysis of the role of Csw in the EGFR signaling pathway.
Johnson Hamlet
M R
MR
Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Perkins
L A
LA
D000818:Animals; D030801:Animals, Genetically Modified; D003433:Crosses, Genetic; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins; D066246:ErbB Receptors / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics; D007150:Immunohistochemistry; D008648:Mesoderm / Q000378:metabolism; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics; D015398:Signal Transduction; D014018:Tissue Distribution; D018631:ras Proteins
D029721:Drosophila Proteins; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D066246:ErbB Receptors; D016392:Proto-Oncogene Proteins pp60(c-src); C098692:Csw protein, Drosophila; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D019204:GTP-Binding Proteins; C417283:Ras85D protein, Drosophila; D018631:ras Proteins