title: JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, La Jolla 92093-0636.
authors.forename: T
authors.initials: T
authors.lastname: Kallunki
authors.forename: B
authors.initials: B
authors.lastname: Su
authors.forename: I
authors.initials: I
authors.lastname: Tsigelny
authors.forename: H K
authors.initials: HK
authors.lastname: Sluss
authors.forename: B
authors.initials: B
authors.lastname: Dérijard
authors.forename: G
authors.initials: G
authors.lastname: Moore
authors.forename: R
authors.initials: R
authors.lastname: Davis
authors.forename: M
authors.initials: M
authors.lastname: Karin
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D015870:Gene Expression; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011494:Protein Kinases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D011494:Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases