ArticleProceedings of the National Academy of Sciences of the United States of America2015
Structure and dynamics of the MKK7-JNK signaling complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
- Alternative Splicing of a Structured Partner Alters the Folding-Upon-Binding Trajectory of an Intrinsically Disordered Protein.Journal of the American Chemical Society · 2026Article
- ERK autoinhibition mechanism informs a drug combination strategy.Protein science : a publication of the Protein Society · 2026Article
- Lactucopicrin promotes the autophagic degradation of MAP2K4/MKK4 by mediating CCDC50 palmitoylation to alleviate osteoarthritis progression.Autophagy · 2026Article
- Hierarchical folding-upon-binding of an intrinsically disordered protein.Nature communications · 2025Article
- Sequence- and Docking-Site-Dependent Contributions to Multi-Site Phosphorylation of an Intrinsically Disordered MAPK Substrate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Fuzziness in enzymatic catalysis.Current opinion in structural biology · 2025Review
- Bipartite binding of the intrinsically disordered scaffold protein JIP1 to the kinase JNK1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular Bidents with Two Electrophilic Warheads as a New Pharmacological Modality.ACS central science · 2024Article
- The Role of the Dysregulated JNK Signaling Pathway in the Pathogenesis of Human Diseases and Its Potential Therapeutic Strategies: A Comprehensive Review.Biomolecules · 2024Review
- Linear motif specificity in signaling through p38α and ERK2 mitogen-activated protein kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors.Science signaling · 2023Article
- The optimal docking strength for reversibly tethered kinases.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- NMR Provides Unique Insight into the Functional Dynamics and Interactions of Intrinsically Disordered Proteins.Chemical reviews · 2022Review
- Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs.The Biochemical journal · 2022Review
- Crystallographic mining of ASK1 regulators to unravel the intricate PPI interfaces for the discovery of small molecule.Computational and structural biotechnology journal · 2022Review
- Synergies of Single Molecule Fluorescence and NMR for the Study of Intrinsically Disordered Proteins.Biomolecules · 2021Review
- Enthalpy-Entropy Compensation in the Promiscuous Interaction of an Intrinsically Disordered Protein with Homologous Protein Partners.Biomolecules · 2021Article
- The Map3k12 (Dlk)/JNK3 signaling pathway is required for pancreatic beta-cell proliferation during postnatal development.Cellular and molecular life sciences : CMLS · 2021Article
- miR-331-3p is involved in glucocorticoid resistance reversion by rapamycin through suppression of the MAPK signaling pathway.Cancer chemotherapy and pharmacology · 2020Article
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Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling specificity in the mitogen-activated protein kinase (MAPK) pathways is controlled by disordered domains of the MAPK kinases (MKKs) that specifically bind to their cognate MAPKs via linear docking motifs. MKK7 activates the c-Jun N-terminal kinase (JNK) pathway and is the only MKK containing three motifs within its regulatory domain. Here, we characterize the conformational behavior and interaction mechanism of the MKK7 regulatory domain. Using NMR spectroscopy, we develop an atomic resolution ensemble description of MKK7, revealing highly diverse intrinsic conformational propensities of the three docking sites, suggesting that prerecognition sampling of the bound-state conformation is not prerequisite for binding. Although the different sites exhibit similar affinities for JNK1, interaction kinetics differ considerably. Importantly, we determine the crystal structure of JNK1 in complex with the second docking site of MKK7, revealing two different binding modes of the docking motif correlating with observations from NMR exchange spectroscopy. Our results provide unique insight into how signaling specificity is regulated by linear motifs and, in general, into the role of conformational disorder in MAPK signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.