ArticleeLife2024
Structure and function of the ROR2 cysteine-rich domain in vertebrate noncanonical WNT5A signaling.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- Review
- The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling.Biochemical Society transactions · 2026Review
- Conformational cycling of the Wntless transporter drives trafficking and secretion of Wnt morphogens.Nature communications · 2026Article
- Dishevelled PDZ domain targeting peptides modulate non-canonical Wnt5a/Ror signaling.Biochemistry and biophysics reports · 2026Article
- Article
- CryptoBank: A resource for the identification and prediction of cryptic sites in proteins.Science advances · 2026Article
- Towards a phylogenetically informed approach to solving protein-protein interactions.Biochemical Society transactions · 2025Review
- Identification of Wnt-5a Receptors Important in Diabetic and Non-Diabetic Corneal Epithelial Wound Healing.Investigative ophthalmology & visual science · 2025Article
- An Efficient Method for Immortalizing Mouse Embryonic Fibroblasts by CRISPR-mediated Deletion of theBio-protocol · 2025Article
- Review
- Novel biomarkers and drug correlations of non-canonical WNT signaling in prostate and breast cancer.Discover oncology · 2024Article
- An efficient method for immortalizing mouse embryonic fibroblasts.bioRxiv : the preprint server for biology · 2024Article
- Structure and function of the ROR2 cysteine-rich domain in vertebrate noncanonical WNT5A signaling.eLife · 2024Article
- Non-canonical WNT5A-ROR signaling: New perspectives on an ancient developmental pathway.Current topics in developmental biology · 2023Article
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Authors and funding
10 authors.
Funding
Abstract
The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, brachydactyly B, and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.
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