{"doi":"10.1101/2020.06.22.163790","title":"Proteomic analysis identifies the E3 ubiquitin ligase Pdzrn3 as a regulatory target of Wnt5a-Ror signaling","abstract":"Abstract Wnt5a-Ror signaling is a conserved pathway that regulates morphogenetic processes during vertebrate development, but its downstream signaling events remain poorly understood. Through a large-scale proteomic screen in mouse embryonic fibroblasts, we identified the E3 ubiquitin ligase Pdzrn3 as a regulatory target of the Wnt5a-Ror pathway. Upon pathway activation, Pdzrn3 is degraded in a β-catenin-independent, ubiquitin-proteasome system-dependent manner. We developed a flow cytometry-based reporter to monitor Pdzrn3 abundance and delineated a signaling cascade involving Frizzled, Dishevelled, CK1, and GSK3 that regulates Pdzrn3 stability. Epistatically, Pdzrn3 is regulated independently of Kif26b, another Wnt5a-Ror effector. Wnt5a-dependent degradation of Pdzrn3 requires phosphorylation of three conserved amino acids within its C-terminal LNX3H domain, which acts as a bona fide Wnt5a-responsive element. Importantly, this phospho-dependent degradation is essential for Wnt5a-Ror modulation of cell migration. Collectively, this work establishes a new Wnt5a-Ror cell morphogenetic cascade involving Pdzrn3 phosphorylation and degradation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126947,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":574992,"name":"Michael W. Susman","orcid":"0000-0001-8635-283X","position":1,"is_corresponding":false},{"id":575429,"name":"Ryan C. Kunz","orcid":null,"position":2,"is_corresponding":false},{"id":574993,"name":"Jia Tan","orcid":"0000-0002-2079-6937","position":3,"is_corresponding":false},{"id":574994,"name":"Srisathya Srinivasan","orcid":"0000-0002-4502-5063","position":4,"is_corresponding":false},{"id":53296,"name":"Michael D. Cohen","orcid":"0000-0001-6557-2075","position":5,"is_corresponding":false},{"id":378280,"name":"Kyoko Okada","orcid":"0000-0001-6459-7481","position":6,"is_corresponding":false},{"id":574995,"name":"Helen Lamb","orcid":"0000-0002-4425-7014","position":7,"is_corresponding":false},{"id":228589,"name":"S. S. Choi","orcid":"0000-0003-1644-3407","position":8,"is_corresponding":false},{"id":574996,"name":"Edith P. Karuna","orcid":"0000-0002-7292-9009","position":9,"is_corresponding":false},{"id":333389,"name":"Michael K. Scales","orcid":"0000-0002-3645-5643","position":10,"is_corresponding":false},{"id":107041,"name":"Steven P. Gygi","orcid":"0000-0001-7626-0034","position":11,"is_corresponding":false},{"id":85691,"name":"Michael E. Greenberg","orcid":"0000-0003-1380-2160","position":12,"is_corresponding":false},{"id":356251,"name":"Hsin‐Yi Henry Ho","orcid":"0000-0002-8780-7864","position":13,"is_corresponding":false},{"id":574991,"name":"Sara E. Konopelski","orcid":"0000-0002-7060-3398","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}