Genetic and molecular analyses of mutations involved in Drosophila raf signal transduction.
We have identified dominant mutations that suppress the lethality associated with an R217-->L mutation in the GTP.Ras binding region (CR1) of the Drosophila raf (D-raf) serine/threonine kinase. Four intragenic and seven extragenic suppressors were recovered. Each of the four intragenic mutations contains one compensatory amino acid change located in either the CR1 or the kinase domain of D-raf. The seven extragenic suppressors represent at least four genetic loci whose effects strongly suggest that they participate in both the sevenless and Drosophila EGF receptor (DER) signaling pathways. One of these mutations, Su(D-raf)34B, is an allele of D-mek which encodes the known signaling molecule MAPK kinase (MEK). A D83V mutation in D-MEK is identified and shown to be sufficient to confer the dominant activity of Su(D-raf)34B.
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Department of Genetics, Howard Hughes Medical Institute, Boston, MA 02115.
Melnick
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Hsu
J C
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Perrimon
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N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005123:Eye / Q000196:embryology / Q000254:growth & development; D005260:Female; D017344:Genes, Insect / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics*; D009866:Oogenesis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D013489:Suppression, Genetic / Q000235:genetics*
D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases