14-3-3 epsilon positively regulates Ras-mediated signaling in Drosophila.
We have isolated mutations in the gene encoding a Drosophila 14-3-3 epsilon protein as suppressors of the rough eye phenotype caused by the ectopic expression of RAS1(V12). Using a simple loss-of-function 14-3-3 epsilon mutation, we show that 14-3-3 epsilon acts to increase the efficiency of RAS1 signaling. The 14-3-3 epsilon protein appears to function in multiple RTK pathways, suggesting that it is a general component of RAS1 signaling cascade. Sequence analysis of three dominant-negative alleles defines two regions of 14-3-3 epsilon that participate in RAS1 signaling. We also present evidence that 14-3-3 epsilon and 14-3-3 zeta, two 14-3-3 protein family members, are partially redundant for RAS1 signaling in photoreceptor formation and in animal viability. Our genetic data suggest that 14-3-3 epsilon functions downstream of or parallel to RAF, but upstream of nuclear factors in RAS1 signaling.
Chang
H C
HC
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley 94720-3200, USA.
Rubin
G M
GM
D048948:14-3-3 Proteins; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D005123:Eye / Q000033:anatomy & histology; D017344:Genes, Insect; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013489:Suppression, Genetic; D014446:Tyrosine 3-Monooxygenase; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
D048948:14-3-3 Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins