Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase

Science. 1998 May 22;280(5367):1262-5. doi: 10.1126/science.280.5367.1262.

Abstract

MAP kinase phosphatase-3 (MKP-3) dephosphorylates phosphotyrosine and phosphothreonine and inactivates selectively ERK family mitogen-activated protein (MAP) kinases. MKP-3 was activated by direct binding to purified ERK2. Activation was independent of protein kinase activity and required binding of ERK2 to the noncatalytic amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker ERK2 mutant D319N nor c-Jun amino-terminal kinase-stress-activated protein kinase (JNK/SAPK) or p38 MAP kinases bound MKP-3 or caused its catalytic activation. These kinases were also resistant to enzymatic inactivation by MKP-3. Another homologous but nonselective phosphatase, MKP-4, bound and was activated by ERK2, JNK/SAPK, and p38 MAP kinases. Catalytic activation of MAP kinase phosphatases through substrate binding may regulate MAP kinase activation by a large number of receptor systems.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Catalysis
  • Dual Specificity Phosphatase 6
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 12
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Transfection
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Recombinant Fusion Proteins
  • Epidermal Growth Factor
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 12
  • Mitogen-Activated Protein Kinase 9
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Dual Specificity Phosphatase 6
  • Protein Tyrosine Phosphatases