{"doi":"10.1074/jbc.m111.317578","title":"Galactose Differentially Modulates Lunatic and Manic Fringe Effects on Delta1-induced NOTCH Signaling","abstract":null,"journal":"Journal of Biological Chemistry","year":2012,"id":595805,"datarank":0.5456379239589579,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":0.0,"self_endowment_contribution":0.5456379239589579,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1244674,"name":"Yuko Tashima","orcid":null,"position":1,"is_corresponding":false},{"id":362372,"name":"Pamela Stanley","orcid":"0000-0001-5704-3747","position":2,"is_corresponding":false},{"id":1525853,"name":"Xinghua Hou","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Galactose Differentially Modulates Lunatic and Manic Fringe Effects on Delta1-induced NOTCH Signaling","abstract":"NOTCH signaling induced by Delta1 (DLL1) and Jagged1 (JAG1) NOTCH ligands is modulated by the β3N-acetylglucosaminyl transferase Fringe. LFNG (Lunatic Fringe) and MFNG (Manic Fringe) transfer N-acetylglucosamine (GlcNAc) to O-fucose attached to EGF-like repeats of NOTCH receptors. In co-culture NOTCH signaling assays, LFNG generally enhances DLL1-induced, but inhibits JAG1-induced, NOTCH signaling. In mutant Chinese hamster ovary (CHO) cells that do not add galactose (Gal) to the GlcNAc transferred by Fringe, JAG1-induced NOTCH signaling is not inhibited by LFNG or MFNG. In mouse embryos lacking B4galt1, NOTCH signaling is subtly reduced during somitogenesis. Here we show that DLL1-induced NOTCH signaling in CHO cells was enhanced by LFNG, but this did not occur in either Lec8 or Lec20 CHO mutants lacking Gal on O-fucose glycans. Lec20 mutants corrected with a B4galt1 cDNA became responsive to LFNG. By contrast, MFNG promoted DLL1-induced NOTCH signaling better in the absence of Gal than in its presence. This effect was reversed in Lec8 cells corrected by expression of a UDP-Gal transporter cDNA. The MFNG effect was abolished by a DDD to DDA mutation that inactivates MFNG GlcNAc transferase activity. The binding of soluble NOTCH ligands and NOTCH1/EGF1–36 generally reflected changes in NOTCH signaling caused by LFNG and MFNG. Therefore, the presence of Gal on O-fucose glycans differentially affects DLL1-induced NOTCH signaling modulated by LFNG versus MFNG. Gal enhances the effect of LFNG but inhibits the effect of MFNG on DLL1-induced NOTCH signaling, with functional consequences for regulating the strength of NOTCH signaling. NOTCH signaling induced by Delta1 (DLL1) and Jagged1 (JAG1) NOTCH ligands is modulated by the β3N-acetylglucosaminyl transferase Fringe. LFNG (Lunatic Fringe) and MFNG (Manic Fringe) transfer N-acetylglucosamine (GlcNAc) to O-fucose attached to EGF-like repeats of NOTCH receptors. In co-culture NOTCH signaling assays, LFNG generally enhances DLL1-induced, but inhibits JAG1-induced, NOTCH signaling. In mutant Chinese hamster ovary (CHO) cells that do not add galactose (Gal) to the GlcNAc transferred by Fringe, JAG1-induced NOTCH signaling is not inhibited by LFNG or MFNG. In mouse embryos lacking B4galt1, NOTCH signaling is subtly reduced during somitogenesis. Here we show that DLL1-induced NOTCH signaling in CHO cells was enhanced by LFNG, but this did not occur in either Lec8 or Lec20 CHO mutants lacking Gal on O-fucose glycans. Lec20 mutants corrected with a B4galt1 cDNA became responsive to LFNG. By contrast, MFNG promoted DLL1-induced NOTCH signaling better in the absence of Gal than in its presence. This effect was reversed in Lec8 cells corrected by expression of a UDP-Gal transporter cDNA. The MFNG effect was abolished by a DDD to DDA mutation that inactivates MFNG GlcNAc transferase activity. The binding of soluble NOTCH ligands and NOTCH1/EGF1–36 generally reflected changes in NOTCH signaling caused by LFNG and MFNG. Therefore, the presence of Gal on O-fucose glycans differentially affects DLL1-induced NOTCH signaling modulated by LFNG versus MFNG. Gal enhances the effect of LFNG but inhibits the effect of MFNG on DLL1-induced NOTCH signaling, with functional consequences for regulating the strength of NOTCH signaling.","is_dataset_classified":null,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22081605","pmcid":"PMC3249100","openalex_id":"https://openalex.org/W2043209260","authors":[],"funders":[{"funder_name":"PHS HHS","grant_id":"P01 13330","title":null},{"funder_name":"PHS HHS","grant_id":"R01 95022","title":null}],"total_grants":2,"fwci":2.2225,"citation_percentile":0.87883834,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":2},{"year":2014,"count":8},{"year":2015,"count":1},{"year":2016,"count":1},{"year":2017,"count":5},{"year":2018,"count":4},{"year":2019,"count":2},{"year":2020,"count":5},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2025,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820535308/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820535308/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820535308?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820535308?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M111.317578","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m111.317578","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22081605","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3249100","host_type":"repository"}],"fields_of_study":["Animal Genetics and Reproduction","Developmental Biology and Gene Regulation","Congenital heart defects research"],"mesh_terms":["Serrate-Jagged Proteins","Jagged-1 Protein","Animals","Calcium-Binding Proteins","Cricetulus","Epidermal Growth Factor","Extracellular Space","Galactose","Glucosyltransferases","Cricetinae","Membrane Proteins","Polysaccharides","Proteins","Solubility","Signal Transduction","CHO Cells","Glycosyltransferases","Protein Structure, Tertiary","Intercellular Signaling Peptides and Proteins","Intracellular Signaling Peptides and Proteins","Mice","Receptors, Notch"],"keywords":["Notch signaling pathway","JAG1","Somitogenesis","Cell biology","Notch proteins","Biology","Fucose","Molecular biology","Mutant","Chemistry","Signal transduction","Biochemistry","Gene","Glycoprotein"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T17:54:23.078261Z","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":[]}