Abstract
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.
MeSH terms
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Amino Acid Sequence
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Differentiation
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Cloning, Molecular
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Cytoplasm / enzymology
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Cytoplasm / metabolism
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Down-Regulation
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Drosophila Proteins*
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Drosophila melanogaster / cytology
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Drosophila melanogaster / enzymology*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / growth & development
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Enzyme Activation
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Eye / enzymology
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Eye / growth & development
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Eye / metabolism
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Gene Expression
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Genes, Insect / genetics
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Molecular Sequence Data
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Mutation
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Phenotype
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Phosphorylation
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Photoreceptor Cells, Invertebrate / cytology*
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Proto-Oncogene Proteins p21(ras) / genetics
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Proto-Oncogene Proteins p21(ras) / metabolism*
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Signal Transduction
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Suppression, Genetic
Substances
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Drosophila Proteins
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Calcium-Calmodulin-Dependent Protein Kinases
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PTP-ER protein, Drosophila
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Protein Tyrosine Phosphatases
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Proto-Oncogene Proteins p21(ras)