MKP-8, a novel MAPK phosphatase that inhibits p38 kinase

Biochem Biophys Res Commun. 2005 May 6;330(2):511-8. doi: 10.1016/j.bbrc.2005.03.028.


Intracellular signaling pathways and their relationship to malignant progression have become a major focus of cancer biology. The dual-specificity phosphatase (DSP) family is a more recently identified family of intracellular signaling modulators. We have identified a novel protein phosphatase with a well-conserved DSP catalytic domain containing the DSP catalytic motif, xHCxxGxSRS, and mitogen-activated protein kinase phosphatase (MKP) motif, AYLM. Because of these unique characteristics, the protein was named mitogen-activated protein kinase phosphatase-8 (MKP-8). This protein is approximately 20kDa in size and mainly localizes to the nuclear compartment of the cell. MKP-8 is expressed in embryonal cancers (retinoblastoma, neuroepithelioma, and neuroblastoma) and has limited expression in normal tissues. MKP-8 displays significant phosphatase activity that is inhibited by a cysteine to serine substitution in the catalytic domain. When co-expressed with activated MAPKs, MKP-8 is able to inhibit p38 kinase phosphorylation and downstream activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Catalytic Domain
  • Cloning, Molecular
  • DNA Primers
  • Dual-Specificity Phosphatases
  • Humans
  • Mitogen-Activated Protein Kinase Phosphatases
  • Molecular Sequence Data
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / physiology*
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / chemistry


  • DNA Primers
  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Phosphatases
  • DUSP26 protein, human
  • Dual-Specificity Phosphatases
  • Protein Tyrosine Phosphatases