ArticleProceedings of the National Academy of Sciences of the United States of America2017
Local destabilization, rigid body, and fuzzy docking facilitate the phosphorylation of the transcription factor Ets-1 by the mitogen-activated protein kinase ERK2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed.
- 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
- An exploratory analysis of bezisterim treatment associated with decreased biological age acceleration, and improved clinical measure and biomarker changes in mild-to-moderate probable Alzheimer's disease.Frontiers in neuroscience · 2025Article
- 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
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Conformational states dynamically populated by a kinase determine its function.Science (New York, N.Y.) · 2020Article
- MAP Kinase-Mediated Activation of RSK1 and MK2 Substrate Kinases.Structure (London, England : 1993) · 2020Article
- ERK signalling: a master regulator of cell behaviour, life and fate.Nature reviews. Molecular cell biology · 2020Review
- Ets1 functions partially redundantly with Etv2 to promote embryonic vasculogenesis and angiogenesis in zebrafish.Developmental biology · 2020Article
- Activation Loop Dynamics Are Coupled to Core Motions in Extracellular Signal-Regulated Kinase-2.Biochemistry · 2020Article
- The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight.Frontiers in oncology · 2020Review
- Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo.Nature communications · 2019Article
- Extracellular Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Gene Expression.International journal of molecular sciences · 2019Review
- A Novel Class of Common Docking Domain Inhibitors That Prevent ERK2 Activation and Substrate Phosphorylation.ACS chemical biology · 2019Article
- Design, synthesis and biological evaluation of fused naphthofuro[3,2-c] quinoline-6,7,12-triones and pyrano[3,2-c]quinoline-6,7,8,13-tetraones derivatives as ERK inhibitors with efficacy in BRAF-mutant melanoma.Bioorganic chemistry · 2019Article
- Specificity of Phosphorylation Responses to Mitogen Activated Protein (MAP) Kinase Pathway Inhibitors in Melanoma Cells.Molecular & cellular proteomics : MCP · 2018Article
- Measuring the signs of the methylJournal of biomolecular NMR · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Mitogen-activated protein (MAP) kinase substrates are believed to require consensus docking motifs (D-site, F-site) to engage and facilitate efficient site-specific phosphorylation at specific serine/threonine-proline sequences by their cognate kinases. In contrast to other MAP kinase substrates, the transcription factor Ets-1 has no canonical docking motifs, yet it is efficiently phosphorylated by the MAP kinase ERK2 at a consensus threonine site (T38). Using NMR methodology, we demonstrate that this phosphorylation is enabled by a unique bipartite mode of ERK2 engagement by Ets-1 and involves two suboptimal noncanonical docking interactions instead of a single canonical docking motif. The N terminus of Ets-1 interacts with a part of the ERK2 D-recruitment site that normally accommodates the hydrophobic sidechains of a canonical D-site, retaining a significant degree of disorder in its ERK2-bound state. In contrast, the C-terminal region of Ets-1, including its Pointed (PNT) domain, engages in a largely rigid body interaction with a section of the ERK2 F-recruitment site through a binding mode that deviates significantly from that of a canonical F-site. This latter interaction is notable for the destabilization of a flexible helix that bridges the phospho-acceptor site to the rigid PNT domain. These two spatially distinct, individually weak docking interactions facilitate the highly specific recognition of ERK2 by Ets-1, and enable the optimal localization of its dynamic phospho-acceptor T38 at the kinase active site to enable efficient phosphorylation.
Indexed as
Identifiers
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.