Control of cell fate determination by p21ras/Ras1, an essential component of torso signaling in Drosophila.
Determination of cell fate at the posterior termini of the Drosophila embryo is specified by the activation of the torso (tor) receptor tyrosine kinase. This signaling pathway is mediated by the serine/threonine kinase D-raf and a protein tyrosine phosphatase corkscrew (csw). We found that expression of an activated form of Ras1 during oogenesis resulted in embryos with tor gain-of-function phenotypes. To demonstrate that p21ras/Ras1 mediates tor signaling, we injected mammalian p21ras variants into early Drosophila embryos. We found that the injection of activated p21v-ras rescued the maternal-effect phenotypes of both tor and csw null mutations. These rescuing effects of p21v-ras are dependent on the presence of maternally derived D-raf activity. In addition, wild-type embryos show a terminal-class phenotype resembling csw when injected with p21rasN17, a dominant-negative form of p21ras. Furthermore, we have analyzed the maternal-effect phenotype of Son of sevenless (Sos), a positive regulator of Ras1, and showed that embryos derived from germ cells lacking Sos+ activity exhibit a terminal-class phenotype. Our study demonstrates that the Drosophila p21ras, encoded by Ras1, is an intrinsic component of the tor signaling pathway, where it is both necessary and sufficient in specifying posterior terminal cell fates. p21ras/Ras1 operates upstream of the D-raf kinase in this signaling pathway.
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Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Chou
T B
TB
Williams
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Roberts
T
T
Perrimon
N
N
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002970:Cleavage Stage, Ovum; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D017344:Genes, Insect; D011905:Genes, ras; D007301:Insect Hormones / Q000235:genetics / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009024:Morphogenesis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D020664:Son of Sevenless Proteins
D029721:Drosophila Proteins; D007301:Insect Hormones; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D020664:Son of Sevenless Proteins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C080148:tor protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017027:Protein Tyrosine Phosphatases; D016283:Proto-Oncogene Proteins p21(ras)