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JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation.
Open accessAbstract
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.
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“Almost 20 years ago, it was discovered that MAPKs contain a docking site in the C-terminal lobe that binds a conserved 13-16 amino acid sequence known as the D-or KIM-motif (kinase interaction motif).”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [19]
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Metadata
- Authors
- Kallunki, T., Su, B., Tsigelny, I., Sluss, H. K., Dérijard, B., Moore, G., Davis, R., & Karin, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1994-12-15
- Volume
- 8
- Issue
- 24
- Pages
- 2996-3007
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W1972145919
- Cited by
- 642
- References
- 34
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 6 · 2014: 15 · 2013: 15 · 2012: 21
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- JNK2, c-Jun, c-Jun N-terminal kinase, mitogen-activated protein kinase, substrate specificity, protein-protein interaction, c-Jun phosphorylation, docking site, catalytic pocket, JNK1, transcriptional activation, gene cloning
- MeSH terms
- Amino Acid Sequence, Binding Sites, Cell Line, Cloning, Molecular, Humans, Kinetics, Models, Molecular, Molecular Sequence Data, Molecular Weight, Protein Kinases, Transfection, Tumor Cells, Cultured, Gene Expression, Proto-Oncogene Proteins c-jun, Conserved Sequence, Sequence Homology, Amino Acid, Protein Structure, Secondary, Calcium-Calmodulin-Dependent Protein Kinases, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 9
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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