Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase.
We have conducted a genetic screen for mutations that decrease the effectiveness of signaling by a protein tyrosine kinase, the product of the Drosophila melanogaster sevenless gene. These mutations define seven genes whose wild-type products may be required for signaling by sevenless. Four of the seven genes also appear to be essential for signaling by a second protein tyrosine kinase, the product of the Ellipse gene. The putative products of two of these seven genes have been identified. One encodes a ras protein. The other locus encodes a protein that is homologous to the S. cerevisiae CDC25 protein, an activator of guanine nucleotide exchange by ras proteins. These results suggest that the stimulation of ras protein activity is a key element in the signaling by sevenless and Ellipse and that this stimulation may be achieved by activating the exchange of GTP for bound GDP by the ras protein.
Simon
M A
MA
Howard Hughes Medical Institute, University of California, Berkeley 94720.
Bowtell
D D
DD
Dodson
G S
GS
Laverty
T R
TR
Rubin
G M
GM
D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D005796:Genes; D020662:Guanine Nucleotide Exchange Factors; D008562:Membrane Glycoproteins / Q000502:physiology*; D008969:Molecular Sequence Data; D010786:Photoreceptor Cells / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics; D016415:Sequence Alignment; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D020663:ras Guanine Nucleotide Exchange Factors
D029721:Drosophila Proteins; D005136:Eye Proteins; D020662:Guanine Nucleotide Exchange Factors; D008562:Membrane Glycoproteins; D011506:Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras)