The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling.
Extracellular growth factors are required for the survival of most animal cells. They often signal through the activation of the Ras pathway. However, the molecular mechanisms by which Ras signaling inhibits the intrinsic cell death machinery are not well understood. Here, we present evidence that in Drosophila, activation of the Ras pathway specifically inhibits the proapoptotic activity of the gene head involution defective (hid). By using transgenic animals and cultured cells, we show that MAPK phosphorylation sites in Hid are critical for this response. These findings define a novel mechanism by which growth factor signaling directly inactivates a critical component of the intrinsic cell death machinery. These studies provide further insights into the function of ras as an oncogene.
Bergmann
A
A
Massachusetts Institute of Technology, Howard Hughes Medical Institute, Department of Biology, Cambridge 02139, USA.
Agapite
J
J
McCall
K
K
Steller
H
H
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases; D005123:Eye / Q000166:cytology; D005804:Genes, Lethal; D016153:Genes, Suppressor; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D019476:Insect Proteins; D009479:Neuropeptides; D010455:Peptides; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C086795:rl protein, Drosophila; D018631:ras Proteins