Modular structure of a docking surface on MAPK phosphatases

J Biol Chem. 2002 Jun 21;277(25):22942-9. doi: 10.1074/jbc.M202096200. Epub 2002 Apr 12.


Mitogen-activated protein kinases (MAPKs) must be precisely inactivated to achieve proper functions in the cells. Ten members of dual specificity phosphatases specifically acting on MAPKs, termed MAPK phosphatases (MKPs), have been reported. Each member has its own substrate specificity that should be tightly regulated. However, the molecular mechanism underlying the regulation of the specificity is largely unknown. In the MAPK signaling pathways, docking interactions, which are different from transient enzyme-substrate interaction, are known to regulate the enzymatic specificity. Here we have identified and characterized a docking surface of MKPs. Our results show that a docking surface is composed of a tandem alignment of three subregions (modules): a cluster of positively charged amino acids, a cluster of hydrophobic amino acids, and a cluster of positively charged amino acids (positive-hydrophobic-positive). This modular structure well fits the docking groove on MAPKs that we have previously identified and may contribute to regulating the docking specificity of the MKP family. The position, number, and species of charged amino acids in each module including the central hydrophobic subregion are important factors in regulation of docking to specific MAPKs. This modular structure in the docking interaction may define a novel model of protein-protein interaction that would also regulate other systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Animals
  • Arginine / chemistry
  • Binding Sites
  • COS Cells
  • Cell Cycle Proteins*
  • Cell Line
  • Dual Specificity Phosphatase 1
  • Humans
  • Immediate-Early Proteins / metabolism
  • MAP Kinase Signaling System
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Mutagenesis
  • Phosphoprotein Phosphatases*
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Phosphatase 1
  • Protein Structure, Tertiary
  • Protein Tyrosine Phosphatases / metabolism*
  • Rats
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Substrate Specificity
  • p38 Mitogen-Activated Protein Kinases


  • Amino Acids
  • Cell Cycle Proteins
  • Immediate-Early Proteins
  • Arginine
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • DUSP1 protein, human
  • Dual Specificity Phosphatase 1
  • Dusp1 protein, mouse
  • Dusp1 protein, rat
  • Protein Tyrosine Phosphatases