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http://purl.uniprot.org/citations/11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11907042http://www.w3.org/2000/01/rdf-schema#comment"Rat surfactant protein C (SP-C) is synthesized as a 194-amino acid propeptide (SP-C-(1-194)) that is directed to the distal secretory pathway and proteolytically processed as an integral membrane protein to yield its mature form. We had shown previously that trafficking of proSP-C is mediated both by a signal anchor domain contained within the mature SP-C sequence and by a targeting domain in the NH(2)-flanking propeptide. Based on evidence from other integral membrane proteins, we hypothesized that proSP-C targeting is effected by oligomerization of proSP-C monomers. To evaluate this in vitro, cDNA constructs encoding for either wild type proSP-C (pcDNA3/SP-C-(1-194)) or heterologous fusion proteins containing green fluorescent protein (EGFP) linked to SP-C-(1-194) (EGFP/SP-C-(1-194)), to mutant proSP-C lacking the NH(2) targeting domain (EGFP/SP-C-(24-194)), or to mature SP-C alone (EGFP/SP-C-(24-58)) were produced. In transfected A549 cells, fluorescence microscopy revealed that pcDNA3/SP-C-(1-194) and EGFP/SP-C-(1-194) were each expressed in CD63 (+), EEA1 (-) cytoplasmic vesicles. Expression of EGFP/SP-C-(24-194) or EGFP/SP-C-(24-58) resulted in translocation but retention in early compartments. When co-transfected with pcDNA3/SP-C-(1-194), both EGFP/SP-C-(24-194) and EGFP/SP-C-(24-58) were directed to CD63 (+) vesicles that also contained SP-C-(1-194). In contrast, trafficking of a folding mutant that forms juxtanuclear aggregates, EGFP/SP-C(C122/186G), was not corrected by cotransfection with pcDNA3/SP-C-(1-194). Chemical cross-linking studies of transfected cell lysates with bismaleimidohexane produced multimeric forms of both EGFP/SP-C-(1-194) and EGFP/SP-C-(24-58). These results indicate that sorting involves oligomeric association of proSP-C monomers mediated by the mature SP-C domain. Heteromeric assembly allows wild type proSP-C to facilitate trafficking of SP-C mutants with intact transmembrane domains but lacking targeting signals. We speculate that heterotypic oligomerization of wild type with SP-C folding mutants produces a dominant negative thus contributing to the pathology of chronic lung disease associated with patients heterozygous for mutant SP-C alleles."xsd:string
http://purl.uniprot.org/citations/11907042http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m201537200"xsd:string
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/author"Beers M.F."xsd:string
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/author"Mulugeta S."xsd:string
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/author"Russo S.J."xsd:string
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/author"Wang W.J."xsd:string
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/pages"19929-19937"xsd:string
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/title"Biosynthesis of surfactant protein C (SP-C). Sorting of SP-C proprotein involves homomeric association via a signal anchor domain."xsd:string
http://purl.uniprot.org/citations/11907042http://purl.uniprot.org/core/volume"277"xsd:string
http://purl.uniprot.org/citations/11907042http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11907042
http://purl.uniprot.org/citations/11907042http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/11907042
http://purl.uniprot.org/uniprot/P11685#attribution-ED5623AA6B282C44C0EB03F29736D9F9http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/#_A0A0H2UHI8-mappedCitation-11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/#_A0A0S2Z4Q0-mappedCitation-11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/#_A0A8I6AKR7-mappedCitation-11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/#_A0A8I6A637-mappedCitation-11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/#_B4DNY9-mappedCitation-11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/#_E5RI64-mappedCitation-11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/#_P11685-mappedCitation-11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/#_P11686-mappedCitation-11907042http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/A0A8I6A637http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/11907042
http://purl.uniprot.org/uniprot/P11686http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/11907042