ArticleiScience2022
Ligands with different dimeric configurations potently activate the EphA2 receptor and reveal its potential for biased signaling.
Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Frequent EPHA2 receptor mutations in cholangiocarcinoma disrupt receptor forward signaling supporting a tumor suppressor role.Biochimica et biophysica acta. Molecular cell research · 2026Article
- Synthetic antibodies targeting EphA2 induce diverse signaling-competent clusters with differential activation.Protein science : a publication of the Protein Society · 2025Article
- Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.Science advances · 2024Article
- Eph receptor signaling complexes in the plasma membrane.Trends in biochemical sciences · 2024Review
- Exploring a Potential Optimization Route for Peptide Ligands of the Sam Domain from the Lipid Phosphatase Ship2.International journal of molecular sciences · 2024Article
- Probing phosphorylation events in biological membranes: The transducer function.Biochimica et biophysica acta. Biomembranes · 2024Review
- Quantitative and qualitative differences in the activation of a fibroblast growth factor receptor by different FGF ligands.Cytokine & growth factor reviews · 2024Review
- Transmembrane helix interactions regulate oligomerization of the receptor tyrosine kinase EphA2.The Journal of biological chemistry · 2024Article
- Limits on the accuracy of contact inhibition of locomotion.Physical review. E · 2024Article
- 2-Pyridone Formation: An Efficient Method for the Solid-Phase Synthesis of Homodimers.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Utility of FRET in studies of membrane protein oligomerization: The concept of the effective dissociation constant.Biophysical journal · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The EphA2 receptor tyrosine kinase activates signaling pathways with different, and sometimes opposite, effects in cancer and other pathologies. Thus, highly specific and potent biased ligands that differentially control EphA2 signaling responses could be therapeutically valuable. Here, we use EphA2-specific monomeric peptides to engineer dimeric ligands with three different geometric configurations to combine a potential ability to differentially modulate EphA2 signaling responses with the high potency and prolonged receptor residence time characteristic of dimeric ligands. The different dimeric peptides readily induce EphA2 clustering, autophosphorylation and signaling, the best with sub-nanomolar potency. Yet, there are differences in two EphA2 signaling responses induced by peptides with different configurations, which exhibit distinct potency and efficacy. The peptides bias signaling when compared with the ephrinA1-Fc ligand and do so via different mechanisms. These findings provide insights into Eph receptor signaling, and proof-of-principle that different Eph signaling responses can be distinctly modulated.
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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 Socratic graph.