PTP-ER, a novel tyrosine phosphatase, functions downstream of Ras1 to downregulate MAP kinase during Drosophila eye development.
Activation of ERK/MAPK is a key event downstream of RAS. The duration, extent, and timing of MAPK activity is integral to signal specificity. Consequently, inactivation of MAPK by phosphatases has emerged as a critical element in the precise control of signal output. We have cloned and characterized a novel cytoplasmic protein tyrosine phosphatase, PTP-ER, which is related to mammalian PCPTP1, LC-PTP/HePTP, and STEP tyrosine phosphatases. PTP-ER mutants produce extra R7 cells and enhance activated Ras1 signaling. Ectopic expression of PTP-ER dramatically inhibits RAS1/MAPK signaling. PTP-ER binds to and inactivates Drosophila ERK/MAPK; however, it is unable to dephosphorylate and downregulate Drosophila MAPKSevenmaker. Resistance to PTP-ER activity partially accounts for the Sevenmaker mutant phenotype.
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism; D015536:Down-Regulation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D004789:Enzyme Activation; D005123:Eye / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D015870:Gene Expression; D017344:Genes, Insect / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology*; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013489:Suppression, Genetic
D029721:Drosophila Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C490690:PTP-ER protein, Drosophila; D017027:Protein Tyrosine Phosphatases; D016283:Proto-Oncogene Proteins p21(ras)