ArticleNature communications2013
Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK.
Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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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Who cites it
52 citing papers in PubMed, 109 citations in OpenAlex.
- ERK autoinhibition mechanism informs a drug combination strategy.Protein science : a publication of the Protein Society · 2026Article
- Molecular identifiers of the evolutionarily conserved titin pseudokinase.The Biochemical journal · 2026Article
- PEA15 promotes osteosarcoma progression and cisplatin resistance by modulating autophagy through the FABP3-TNF signaling axis.iScience · 2025Article
- ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events.Journal of molecular biology · 2025Article
- 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
- A structural atlas of death domain fold proteins reveals their versatile roles in biology and function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Phosphoproteomic response to epidermal growth factor in native rat inner medullary collecting duct.American journal of physiology. Renal physiology · 2025Article
- Molecular interactions between a diphenyl scaffold and PED/PEA15: Implications for type II diabetes therapeutics targeting PED/PEA15 - Phospholipase D1 interaction.Computational and structural biotechnology journal · 2024Article
- ERK1/2 interaction with DHPS regulates eIF5A deoxyhypusination independently of ERK kinase activity.Cell reports · 2024Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2.eLife · 2024Article
- Article
- Activation Loop Plasticity and Active Site Coupling in the MAP Kinase, ERK2.Journal of molecular biology · 2023Article
- Conformation Selection by ATP-competitive Inhibitors and Allosteric Communication in ERK2.bioRxiv : the preprint server for biology · 2023Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Hydrogen peroxide-dependent oxidation of ERK2 within its D-recruitment site alters its substrate selection.iScience · 2023Article
- Not your Mother's MAPKs: Apicomplexan MAPK function in daughter cell budding.PLoS pathogens · 2022Review
- PEA-15 engages in allosteric interactions using a common scaffold in a phosphorylation-dependent manner.Scientific reports · 2022Article
- Phosphorylation of PED/PEA-15 at Ser116 and phosphorylation of p27 at Thr187 indicates a poor prognosis in hepatocellular carcinoma.Oncology letters · 2021Article
- PEA15 loss of function and defective cerebral development in the domestic cat.PLoS genetics · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
ERK1/2 kinases are the principal effectors of a central signalling cascade that converts extracellular stimuli into cell proliferation and migration responses and, when deregulated, can promote cell oncogenic transformation. The scaffolding protein PEA-15 is a death effector domain protein that directly interacts with ERK1/2 and affects ERK1/2 subcellular localization and phosphorylation. Here, to understand this ERK1/2 signalling complex, we have solved the crystal structures of PEA-15 bound to three different ERK2 phospho-conformers. The structures reveal that PEA-15 uses a bipartite binding mode, occupying two key docking sites of ERK2. Remarkably, PEA-15 can efficiently bind the ERK2 activation loop in the critical Thr-X-Tyr region in different phosphorylation states. PEA-15 binding triggers an extended allosteric conduit in dually phosphorylated ERK2, disrupting key features of active ERK2. At the same time PEA-15 binding protects ERK2 from dephosphorylation, thus setting the stage for immediate ERK activity upon its release from the PEA-15 inhibitory complex.
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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.