Molecular identification and functional characterization of a Drosophila dual-specificity phosphatase DMKP-4 which is involved in PGN-induced activation of the JNK pathway

Cell Signal. 2008 Jul;20(7):1329-37. doi: 10.1016/j.cellsig.2008.03.003. Epub 2008 Mar 20.


MAP (Mitogen-activated protein) kinases play an important role in regulating many critical cellular processes. The inactivation of MAP kinases is always accomplished by a family of dual-specificity phosphatases, termed MAPK phosphatases (MKPs). Here, we have identified a novel MKP-like protein, designated DMKP-4, from the Drosophila genome. DMKP-4 is a protein of 387 amino acids, with a dual-specificity phosphatase (DSP) catalytic domain. Recombinant protein DMKP-4 retains intrinsic phosphatase activity against chromogenic substrate pNPP. Overexpression of DMKP-4 inhibited the activation of ERK, JNK and p38 by H(2)O(2), sorbitol and heat shock in HEK293-T cells, and JNK activation in Drosophila S2 cells under PGN stimuli. "Knockdown" of DMKP-4 expression by RNAi significantly enhanced the PGN-stimulated activation of JNK, but not ERK nor p38. Further study revealed that DMKP-4 interacted specifically with JNK via its DSP domain. Mutation of Cys-126 to serine in the DSP domain of DMKP-4 not only eliminated its interaction with JNK, but also markedly reduced its phosphatase activity. Thus, DMKP-4 is a Drosophila homologue of mammalian MKPs, and may play important roles in the regulation of various developmental processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aniline Compounds / metabolism
  • Animals
  • Base Sequence
  • Cell Line
  • Cysteine / genetics
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / enzymology*
  • Dual-Specificity Phosphatases / chemistry
  • Dual-Specificity Phosphatases / genetics
  • Dual-Specificity Phosphatases / metabolism*
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Mutation / genetics
  • Organophosphorus Compounds / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Signal Transduction*
  • Transfection


  • Aniline Compounds
  • Drosophila Proteins
  • Organophosphorus Compounds
  • 4-aminophenylphosphate
  • JNK Mitogen-Activated Protein Kinases
  • Dual-Specificity Phosphatases
  • Cysteine