ArticleProceedings of the National Academy of Sciences of the United States of America2018
Dynamic activation and regulation of the mitogen-activated protein kinase p38.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Mapping of dynamic allostery within p38 alpha kinase via network analyses and NMR spectroscopy.Nature communications · 2026Article
- Structural and dynamic insights into the allosteric activation of p38α MAP kinase via specific docking interactions.Communications biology · 2026Article
- Lipid Pocket Binders Impose Allosteric Changes of Protein Dynamics Around the Active Site of the Protein Kinase p38α.Angewandte Chemie (International ed. in English) · 2026Article
- An optimizedJournal of biomolecular NMR · 2025Article
- Global comparative structural analysis of responses to protein phosphorylation.Nature communications · 2025Article
- Mechanistic insight into the dynamics of Mur ligase through a comprehensive timescale-specific approach.Communications chemistry · 2025Article
- The role of phosphatidylinositol (18:1_18:1) in benign prostatic hyperplasia: an integrated study of Mendelian randomization and network pharmacology.World journal of urology · 2025Article
- Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold.Nature communications · 2024Article
- Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation.bioRxiv : the preprint server for biology · 2024Article
- Identification of a novel aromatic-turmerone analog that activates chaperone-mediated autophagy through the persistent activation of p38.Frontiers in cell and developmental biology · 2024Article
- Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- 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
- Article
- An NMR portrait of functional and dysfunctional allosteric cooperativity in cAMP-dependent protein kinase A.FEBS letters · 2023Review
- Conserved conformational dynamics determine enzyme activity.Science advances · 2022Article
- ATP-competitive inhibitors modulate the substrate binding cooperativity of a kinase by altering its conformational entropy.Science advances · 2022Article
- PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling.Nature communications · 2022Article
- Observation of Arginine Side-Chain Motions Coupled to the Global Conformational Exchange Process in Deubiquitinase A.ACS omega · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Mitogen-activated protein kinases, which include p38, are essential for cell differentiation and autophagy. The current model for p38 activation involves activation-loop phosphorylation with subsequent substrate binding leading to substrate phosphorylation. Despite extensive efforts, the molecular mechanism of activation remains unclear. Here, using NMR spectroscopy, we show how the modulation of protein dynamics across timescales activates p38. We find that activation-loop phosphorylation does not change the average conformation of p38; rather it quenches the loop ps-ns dynamics. We then show that substrate binding to nonphosphorylated and phosphorylated p38 results in uniform µs-ms backbone dynamics at catalytically essential regions and across the entire molecule, respectively. Together, these results show that phosphorylation and substrate binding flatten the energy landscape of the protein, making essential elements of allostery and activation dynamically accessible. The high degree of structural conservation among ser/thr kinases suggests that elements of this mechanism may be conserved across the kinase family.
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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.