The PP2C Alphabet is a negative regulator of stress-activated protein kinase signaling in Drosophila.
The Jun N-terminal kinase and p38 pathways, also known as stress-activated protein kinase (SAPK) pathways, are signaling conduits reiteratively used throughout the development and adult life of metazoans where they play central roles in the control of apoptosis, immune function, and environmental stress responses. We recently identified a Drosophila Ser/Thr phosphatase of the PP2C family, named Alphabet (Alph), which acts as a negative regulator of the Ras/ERK pathway. Here we show that Alph also plays an inhibitory role with respect to Drosophila SAPK signaling during development as well as under stress conditions such as oxidative or genotoxic stresses. Epistasis experiments suggest that Alph acts at a step upstream of the MAPKKs Hep and Lic. Consistent with this interpretation, biochemical experiments identify the upstream MAPKKKs Slpr, Tak1, and Wnd as putative substrates. Together with previous findings, this work identifies Alph as a general attenuator of MAPK signaling in Drosophila.
Baril
Caroline
C
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Sahmi
Malha
M
Ashton-Beaucage
Dariel
D
Stronach
Beth
B
Therrien
Marc
M
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D005124:Eye Abnormalities / Q000235:genetics; D005260:Female; D017344:Genes, Insect; D005804:Genes, Lethal; D005838:Genotype; D020935:MAP Kinase Signaling System; D008297:Male; D008855:Microscopy, Electron, Scanning; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics; D034622:RNA Interference; D015398:Signal Transduction
D017931:DNA Primers; D029721:Drosophila Proteins; D011494:Protein Kinases; C120202:lic protein, Drosophila; C117694:Hep protein, Drosophila; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; C511607:alph protein, Drosophila