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 RIS Download
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