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JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation.

The transcriptional activity of c-Jun is augmented through phosphorylation at two sites by a c-Jun amino-terminal kinase (JNK). All cells express two distinct JNK activities, 46 and 55 kD in size. It is not clear which of them is the more important c-Jun kinase and how they specifically recognize c-Jun. The 46-kD form of JNK was identified as a new member of the MAP kinase group of signal-transducing enzymes, JNK1. Here, we report the molecular cloning of the 55-kD form of JNK, JNK2, which exhibits 83% identity and similar regulation to JNK1. Despite this close similarity, the two JNKs differ greatly in their ability to interact with c-Jun. JNK2 binds c-Jun approximately 25 times more efficiently than JNK1, and as a result has a lower Km toward c-Jun than JNK1. The structural basis for this difference was investigated and traced to a small beta-strand-like region near the catalytic pocket of the enzyme. Modeling suggests that this region is solvent exposed and therefore is likely to serve as a docking site that increases the effective concentration of c-Jun near JNK2. These results explain how two closely related MAP kinases can differ in their ability to recognize specific substrates and thereby elicit different biological responses.

Pubmed ID: 8001819


  • Kallunki T
  • Su B
  • Tsigelny I
  • Sluss HK
  • DĂ©rijard B
  • Moore G
  • Davis R
  • Karin M


Genes & development

Publication Data

December 15, 1994

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence
  • Gene Expression
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Kinetics
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Weight
  • Protein Kinases
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins c-jun
  • Sequence Homology, Amino Acid
  • Transfection
  • Tumor Cells, Cultured