{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li M"],"funding":["Fundamental Research Funds for the Central Universities","NICHD NIH HHS","National Natural Science Foundation of China","National Institutes of Health","NIGMS NIH HHS"],"pagination":["e55873"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10240186"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(6)"],"pubmed_abstract":["The membrane-tethered protease Tiki antagonizes Wnt3a signaling by cleaving and inactivating Wnt3a in Wnt-producing cells. Tiki also functions in Wnt-receiving cells to antagonize Wnt signaling by an unknown mechanism. Here, we demonstrate that Tiki inhibition of Wnt signaling at the cell surface requires Frizzled (FZD) receptors. Tiki associates with the Wnt-FZD complex and cleaves the N-terminus of Wnt3a or Wnt5a, preventing the Wnt-FZD complex from recruiting and activating the coreceptor LRP6 or ROR1/2 without affecting Wnt-FZD complex stability. Intriguingly, we demonstrate that the N-terminus of Wnt3a is required for Wnt3a binding to LRP6 and activating β-catenin signaling, while the N-terminus of Wnt5a is dispensable for recruiting and phosphorylating ROR1/2. Both Tiki enzymatic act"],"journal":["EMBO reports"],"pubmed_title":["Frizzled receptors facilitate Tiki inhibition of Wnt signaling at the cell surface."],"pmcid":["PMC10240186"],"funding_grant_id":["R01GM57603","R35 GM134953","R35GM134953/MIRA","81870620","P50 HD105351","R01 GM057603","2021GCRC033"],"pubmed_authors":["Zheng J","Xu K","He X","Zhang X","Sheng R","MacDonald BT","Li M","Luo D"],"additional_accession":[]},"is_claimable":false,"name":"Frizzled receptors facilitate Tiki inhibition of Wnt signaling at the cell surface.","description":"The membrane-tethered protease Tiki antagonizes Wnt3a signaling by cleaving and inactivating Wnt3a in Wnt-producing cells. Tiki also functions in Wnt-receiving cells to antagonize Wnt signaling by an unknown mechanism. Here, we demonstrate that Tiki inhibition of Wnt signaling at the cell surface requires Frizzled (FZD) receptors. Tiki associates with the Wnt-FZD complex and cleaves the N-terminus of Wnt3a or Wnt5a, preventing the Wnt-FZD complex from recruiting and activating the coreceptor LRP6 or ROR1/2 without affecting Wnt-FZD complex stability. Intriguingly, we demonstrate that the N-terminus of Wnt3a is required for Wnt3a binding to LRP6 and activating β-catenin signaling, while the N-terminus of Wnt5a is dispensable for recruiting and phosphorylating ROR1/2. Both Tiki enzymatic act","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jun","modification":"2026-07-16T12:04:26.944Z","creation":"2025-04-04T20:16:08.552Z"},"accession":"S-EPMC10240186","cross_references":{"pubmed":["36994853"],"doi":["10.15252/embr.202255873"]}}