ArticleScience (New York, N.Y.)2023
Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation.
Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Integrated LiP-MS and quantitative proteomics reveal coordinated alterations in protein conformation and expression across tumor and peritumoral regions in hepatocellular carcinoma.Scientific reports · 2026Article
- A conserved dimerization element is required for protein kinase activation bybioRxiv : the preprint server for biology · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Engineering polyphenol-based osteogenic system for bone and cartilage repair: Transplantation, tissue engineering, and organoid.Journal of advanced research · 2026Review
- Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1.bioRxiv : the preprint server for biology · 2026Article
- Review
- Critical role of the CMGC insert sequence for tyrosine autophosphorylation in the protein kinase DYRK1B.Scientific reports · 2025Article
- Structural basis for MEKK2 dimerization and substrate recognition.Nature communications · 2025Article
- Fuzziness in enzymatic catalysis.Current opinion in structural biology · 2025Review
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification of sinensetin as a selective inhibitor for mitogen-activated protein kinase kinase 6 and an anticancer agent for non-small cell lung cancer.American journal of cancer research · 2025Article
- In silico evaluation of berberine and silymarin against metabolic targets: a rationale for OMICS technology-based co-formulation.In silico pharmacology · 2025Article
- Combinatorial Targeting of Common Docking and ATP Binding Sites on Mps1 MAPK for Management of Pathogenic Fungi.Journal of agricultural and food chemistry · 2024Article
- Special Issue: MAPK Signaling Cascades in Human Health and Diseases.International journal of molecular sciences · 2024Article
- Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation.bioRxiv : the preprint server for biology · 2024Article
- A comprehensive exploration of the druggable conformational space of protein kinases using AI-predicted structures.PLoS computational biology · 2024Article
- Mitogen-activated protein kinase-guided drug discovery for post-viral and related types of lung disease.European respiratory review : an official journal of the European Respiratory Society · 2024Article
- The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox pathway coordination.Nature communications · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
The mitogen-activated protein kinase (MAPK) p38α is a central component of signaling in inflammation and the immune response and is, therefore, an important drug target. Little is known about the molecular mechanism of its activation by double phosphorylation from MAPK kinases (MAP2Ks), because of the challenge of trapping a transient and dynamic heterokinase complex. We applied a multidisciplinary approach to generate a structural model of p38α in complex with its MAP2K, MKK6, and to understand the activation mechanism. Integrating cryo-electron microscopy with molecular dynamics simulations, hydrogen-deuterium exchange mass spectrometry, and experiments in cells, we demonstrate a dynamic, multistep phosphorylation mechanism, identify catalytically relevant interactions, and show that MAP2K-disordered amino termini determine pathway specificity. Our work captures a fundamental step of cell signaling: a kinase phosphorylating its downstream target kinase.
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What OpenQuestion holds
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.