ArticleScientific reports2021
Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 30 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- Dynamic cellular programs of human cardiac allograft rejection revealed by spatial transcriptomics.Nature cardiovascular research · 2026Article
- Infusible Extracellular Matrix Biomaterial Enhances Cell-Specific Pro-Repair Responses Following Acute Myocardial Infarction.Advanced healthcare materials · 2026Article
- Identification of the adhesion GPCR ADGRL4/ELTD1 as a novel potential prognostic biomarker for cerebral cavernous malformation disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- Therapeutic targeting of adhesion GPCRs: a status update and future potential.Expert opinion on drug discovery · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- aGPCR-HEK: A Stable High-Expression Inducible Mammalian Cell Expression System for Adhesion GPCR Structural Biology Applications.Bio-protocol · 2026Article
- Purification of the Active-State G Protein-Coupled Receptor ADGRL4 for Cryo-Electron Microscopy Using a Modular Tag System and a Tethered mini-GBio-protocol · 2026Article
- ADGRD1 promotes bladder cancer progression and angiogenesis via the PI3K/AKT/mTOR-mediated pro-angiogenic secretome.Frontiers in oncology · 2026Article
- GPCR Biased Signaling in Cancer.Handbook of experimental pharmacology · 2026Review
- Synaptic Cell Adhesion: A Structural Perspective.Advances in neurobiology · 2026Review
- Structure of the GNature communications · 2025Article
- Infusible Extracellular Matrix Biomaterial Enhances Cell-Specific Pro-Repair Responses Following Acute Myocardial Infarction.bioRxiv : the preprint server for biology · 2025Article
- Notch activity is modulated by the aGPCR Latrophilin binding the DSL ligand in C. elegans.Nature communications · 2025Article
- Single-cell transcriptomics of clinical grade adipose-derived regenerative cells reveals consistency between donors independent of gender and BMI.Stem cell research & therapy · 2025Article
- Anti-angiogenic effects ofExploration of targeted anti-tumor therapy · 2025Article
- Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis.Science China. Life sciences · 2025Article
- Cellular and Molecular Effects of the Bruck Syndrome-Associated Mutation in theInternational journal of molecular sciences · 2024Article
- A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets for breast cancer.Breast cancer research and treatment · 2024Article
- 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.International journal of molecular sciences · 2024Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
ADGRL4/ELTD1 is an orphan adhesion GPCR (aGPCR) expressed in endothelial cells that regulates tumour angiogenesis. The majority of aGPCRs are orphan receptors. The Stachel Hypothesis proposes a mechanism for aGPCR activation, in which aGPCRs contain a tethered agonist (termed Stachel) C-terminal to the GPCR-proteolytic site (GPS) cleavage point which, when exposed, initiates canonical GPCR signalling. This has been shown in a growing number of aGPCRs. We tested this hypothesis on ADGRL4/ELTD1 by designing full length (FL) and C-terminal fragment (CTF) ADGRL4/ELTD1 constructs, and a range of potential Stachel peptides. Constructs were transfected into HEK293T cells and HTRF FRET, luciferase-reporter and Alphascreen GPCR signalling assays were performed. A stable ADGRL4/ELTD1 overexpressing HUVEC line was additionally generated and angiogenesis assays, signalling assays and transcriptional profiling were performed. ADGRL4/ELTD1 has the lowest GC content in the aGPCR family and codon optimisation significantly increased its expression. FL and CTF ADGRL4/ELTD1 constructs, as well as Stachel peptides, did not activate canonical GPCR signalling. Furthermore, stable overexpression of ADGRL4/ELTD1 in HUVECs induced sprouting angiogenesis, lowered in vitro anastomoses, and decreased proliferation, without activating canonical GPCR signalling or MAPK/ERK, PI3K/AKT, JNK, JAK/HIF-1α, beta catenin or STAT3 pathways. Overexpression upregulated ANTXR1, SLC39A6, HBB, CHRNA, ELMOD1, JAG1 and downregulated DLL4, KIT, CCL15, CYP26B1. ADGRL4/ELTD1 specifically regulates the endothelial tip-cell phenotype through yet undefined signalling pathways.
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