PubMed:15035989 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/15035989","sourcedb":"PubMed","sourceid":"15035989","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/15035989","text":"Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair.\nIncomplete retinal vascularization occurs in both Norrie disease and familial exudative vitreoretinopathy (FEVR). Norrin, the protein product of the Norrie disease gene, is a secreted protein of unknown biochemical function. One form of FEVR is caused by defects in Frizzled-4 (Fz4), a presumptive Wnt receptor. We show here that Norrin and Fz4 function as a ligand-receptor pair based on (1) the similarity in vascular phenotypes caused by Norrin and Fz4 mutations in humans and mice, (2) the specificity and high affinity of Norrin-Fz4 binding, (3) the high efficiency with which Norrin induces Fz4- and Lrp-dependent activation of the classical Wnt pathway, and (4) the signaling defects displayed by disease-associated variants of Norrin and Fz4. These data define a Norrin-Fz4 signaling system that plays a central role in vascular development in the eye and ear, and they indicate that ligands unrelated to Wnts can act through Fz receptors.","tracks":[{"project":"DisGeNET5_gene_disease","denotations":[{"id":"15035989-3#41#51#gene8322","span":{"begin":388,"end":398},"obj":"gene8322"},{"id":"15035989-3#53#56#gene8322","span":{"begin":400,"end":403},"obj":"gene8322"},{"id":"15035989-3#12#16#diseaseC0339539","span":{"begin":359,"end":363},"obj":"diseaseC0339539"}],"relations":[{"id":"41#51#gene832212#16#diseaseC0339539","pred":"associated_with","subj":"15035989-3#41#51#gene8322","obj":"15035989-3#12#16#diseaseC0339539"},{"id":"53#56#gene832212#16#diseaseC0339539","pred":"associated_with","subj":"15035989-3#53#56#gene8322","obj":"15035989-3#12#16#diseaseC0339539"}],"attributes":[{"subj":"15035989-3#41#51#gene8322","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15035989-3#53#56#gene8322","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15035989-3#12#16#diseaseC0339539","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":388,"end":398},"obj":"gene:8322"},{"id":"T1","span":{"begin":359,"end":363},"obj":"disease:C0339539"},{"id":"T2","span":{"begin":400,"end":403},"obj":"gene:8322"},{"id":"T3","span":{"begin":359,"end":363},"obj":"disease:C0339539"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":172,"end":186},"obj":"Disease"},{"id":"T2","span":{"begin":191,"end":227},"obj":"Disease"},{"id":"T3","span":{"begin":229,"end":233},"obj":"Disease"},{"id":"T4","span":{"begin":271,"end":285},"obj":"Disease"},{"id":"T5","span":{"begin":359,"end":363},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0010691"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0019516"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0019516"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0010691"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0019516"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T2","pred":"source","obj":"mondo_disease"},{"subj":"T3","pred":"source","obj":"mondo_disease"},{"subj":"T4","pred":"source","obj":"mondo_disease"},{"subj":"T5","pred":"source","obj":"mondo_disease"}]},{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":602,"end":606},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"10088"},{"subj":"T1","pred":"source","obj":"NCBITAXON"}]},{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":28,"end":34},"obj":"Body_part"},{"id":"T2","span":{"begin":39,"end":48},"obj":"Body_part"},{"id":"T3","span":{"begin":978,"end":981},"obj":"Body_part"},{"id":"T4","span":{"begin":986,"end":989},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000142"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000145"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000140"},{"id":"A4","pred":"mat_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MAT_0000317"},{"id":"A5","pred":"mat_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MAT_0000233"},{"id":"A6","pred":"mat_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MAT_0000138"},{"subj":"T1","pred":"source","obj":"Anatomy-MAT"},{"subj":"T2","pred":"source","obj":"Anatomy-MAT"},{"subj":"T3","pred":"source","obj":"Anatomy-MAT"},{"subj":"T4","pred":"source","obj":"Anatomy-MAT"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":28,"end":34},"obj":"Body_part"},{"id":"T2","span":{"begin":39,"end":48},"obj":"Body_part"},{"id":"T3","span":{"begin":978,"end":981},"obj":"Body_part"},{"id":"T6","span":{"begin":986,"end":989},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000966"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0001846"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000019"},{"id":"A4","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000970"},{"id":"A5","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0010230"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/UBERON_0001690"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":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