ArticleeLife2019
Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 67 citations in OpenAlex.
- Mechanism of and research progress on alterations in the RET gene in thyroid cancer (Review).Molecular medicine reports · 2026Review
- Peptides Targeting GDNF Family Receptor Alpha 1 (GFRα1) Mimic Glial Cell Line-Derived Neurotrophic Factor (GDNF) Bioactivity.Journal of medicinal chemistry · 2026Article
- A long-chain heparan sulfate capture mechanism directs paracrine GDNF-GFRα1 signalling through RET.bioRxiv : the preprint server for biology · 2026Article
- Durable Response to Selpercatinib in Metastatic Colorectal Cancer Harboring a NovelCurrent oncology (Toronto, Ont.) · 2026Article
- De novo and scaffold-based design of GDF15 binders for cancer cachexia diagnostics and therapeutics.Experimental & molecular medicine · 2026Article
- Systematic structure-based analysis of RET variants in MEN2A and Hirschsprung's disease, and the paradoxical co-occurrence of both conditions.Disease models & mechanisms · 2026Article
- RET receptor tyrosine kinase architecture, assemblies, and activation.Endocrine-related cancer · 2026Review
- Proteomics signatures associated with cognitive trajectories: evidence from the English Longitudinal Study of Ageing.medRxiv : the preprint server for health sciences · 2026Article
- Structural insights into the activation of the chicken ROS1 receptor by the NEL/NICOL ligand complex.Nature communications · 2026Article
- Design of Bicyclic Peptide Tandems Mimicking the Homodimeric GDF15 Protein to Inhibit GDF15-GFRaL-RET Complex Cell Signaling.Journal of medicinal chemistry · 2025Article
- GDF15 Analogues Acting as GFRAL Ligands.ChemMedChem · 2025Review
- Exploring the protective effect of metformin against sarcopenia: insights from cohort studies and genetics.Journal of translational medicine · 2025Article
- Mechanisms of resistance to RET-directed therapies.Endocrine-related cancer · 2025Review
- Effective treatment of non-fusion RET intragenic deletion lung adenocarcinoma with pralsetinib: a case report.Frontiers in medicine · 2025Article
- CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly.Nature communications · 2023Article
- Design and Synthesis of Novel Thieno[3,2-ACS omega · 2023Article
- Creation of a Peptide Antagonist of the GFRAL-RET Receptor Complex for the Treatment of GDF15-Induced Malaise.Journal of medicinal chemistry · 2023Article
- Growth differentiation factor 15 induces cisplatin resistance through upregulation of xCT expression and glutathione synthesis in gastric cancer.Cancer science · 2023Article
- Optogenetic dissection of RET signaling reveals robust activation of ERK and enhanced filopodia-like protrusions of regenerating axons.Molecular brain · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
RET is a receptor tyrosine kinase (RTK) that plays essential roles in development and has been implicated in several human diseases. Different from most of RTKs, RET requires not only its cognate ligands but also co-receptors for activation, the mechanisms of which remain unclear due to lack of high-resolution structures of the ligand/co-receptor/receptor complexes. Here, we report cryo-EM structures of the extracellular region ternary complexes of GDF15/GFRAL/RET, GDNF/GFRα1/RET, NRTN/GFRα2/RET and ARTN/GFRα3/RET. These structures reveal that all the four ligand/co-receptor pairs, while using different atomic interactions, induce a specific dimerization mode of RET that is poised to bring the two kinase domains into close proximity for cross-phosphorylation. The NRTN/GFRα2/RET dimeric complex further pack into a tetrameric assembly, which is shown by our cell-based assays to regulate the endocytosis of RET. Our analyses therefore reveal both the common mechanism and diversification in the activation of RET by different ligands.
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.