MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm

Biochem Biophys Res Commun. 2010 Mar 5;393(2):201-6. doi: 10.1016/j.bbrc.2010.01.097. Epub 2010 Feb 1.


MAPK phosphatase-7 (MKP-7) was identified as a JNK-specific phosphatase. However, despite its high specificity for JNK, MKP-7 interacts also with ERK. We previously showed that as a physiological consequence of their interaction, activated ERK phosphorylates MKP-7 at Ser-446, and stabilizing MKP-7. In the present study, we analyzed MKP-7 function in activation of ERK. A time-course experiment showed that both MKP-7 and its phosphatase-dead mutant prolonged mitogen-induced ERK phosphorylation, suggesting that MKP-7 functions as a scaffold for ERK. An important immunohistological finding was that nuclear translocation of phospho-ERK following PMA stimulation was blocked by co-expressed MKP-7 and, moreover, that phospho-ERK co-localized with MKP-7 in the cytoplasm. Reporter gene analysis indicated that MKP-7 blocks ERK-mediated transcription. Overall, our data indicate that MKP-7 down-regulates ERK-dependent gene expression by blocking nuclear accumulation of phospho-ERK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • COS Cells
  • Cell Nucleus / enzymology
  • Chlorocebus aethiops
  • Cytoplasm / enzymology*
  • Down-Regulation
  • Dual-Specificity Phosphatases / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Mitogen-Activated Protein Kinase Phosphatases / metabolism*
  • Phosphorylation
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Transcriptional Activation*


  • Epidermal Growth Factor
  • RPS6KA1 protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase Phosphatases
  • DUSP16 protein, human
  • Dual-Specificity Phosphatases