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.
Howard Hughes Medical Institute, University of California, Berkeley 94720.
M A
MA
Simon
D D
DD
Bowtell
G S
GS
Dodson
T R
TR
Laverty
G M
GM
Rubin
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)