Modulation of the Ras/MAPK signalling pathway by the redox function of selenoproteins in Drosophila melanogaster.
Modulation of reactive oxygen species (ROS) plays a key role in signal transduction pathways. Selenoproteins act controlling the redox balance of the cell. We have studied how the alteration of the redox balance caused by patufet (selD(ptuf)), a null mutation in the Drosophila melanogaster selenophosphate synthetase 1 (sps1) gene, which codes for the SelD enzyme of the selenoprotein biosynthesis, affects the Ras/MAPK signalling pathway. The selD(ptuf) mutation dominantly suppresses the phenotypes in the eye and the wing caused by hyperactivation of the Ras/MAPK cassette and the activated forms of the Drosophila EGF receptor (DER) and Sevenless (Sev) receptor tyrosine kinases (RTKs), which signal in the eye and wing, respectively. No dominant interaction is observed with sensitized conditions in the Wnt, Notch, Insulin-Pi3K, and DPP signalling pathways. Our current hypothesis is that selenoproteins selectively modulate the Ras/MAPK signalling pathway through their antioxidant function. This is further supported by the fact that a selenoprotein-independent increase in ROS caused by the catalase amorphic Cat(n1) allele also reduces Ras/MAPK signalling. Here, we present the first evidence for the role of intracellular redox environment in signalling pathways in Drosophila as a whole organism.
Morey
M
M
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, Barcelona, 08028, Spain.
Serras
F
F
Baguñà
J
J
Hafen
E
E
Corominas
M
M
D000483:Alleles; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases; D005123:Eye / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D005799:Genes, Dominant; D005838:Genotype; D006579:Heterozygote; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D009799:Ocular Physiological Phenomena; D010084:Oxidation-Reduction; D010641:Phenotype; D010770:Phosphotransferases / Q000096:biosynthesis* / Q000235:genetics*; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D051140:Selenoproteins; D015398:Signal Transduction
D000975:Antioxidants; D029721:Drosophila Proteins; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; D017382:Reactive Oxygen Species; D051140:Selenoproteins; D002374:Catalase; D010770:Phosphotransferases; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C086795:rl protein, Drosophila; C062762:selenophosphate synthetase; C109636:sps1 protein, Drosophila; D016283:Proto-Oncogene Proteins p21(ras)