PTP-ER, a novel tyrosine phosphatase, functions downstream of Ras1 to downregulate MAP kinase during Drosophila eye development

Mol Cell. 1999 Jun;3(6):741-50. doi: 10.1016/s1097-2765(01)80006-x.

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

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

Substances

  • Drosophila Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • PTP-ER protein, Drosophila
  • Protein Tyrosine Phosphatases
  • Proto-Oncogene Proteins p21(ras)

Associated data

  • GENBANK/AF146594