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http://purl.uniprot.org/citations/23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23897813http://www.w3.org/2000/01/rdf-schema#comment"Ligand-induced ubiquitylation of EGF receptor (EGFR) is an important regulatory mechanism that controls endocytic trafficking of the receptor and its signaling potential. Here we report that tetraspanin CD82/KAI1 specifically suppresses ubiquitylation of EGFR after stimulation with heparin-binding EGF or amphiregulin and alters the rate of recruitment of the activated receptor to EEA1-positive endosomes. The suppressive effect of CD82 is dependent on the heparin-binding domain of the ligand. Deletion of the C-terminal cytoplasmic domain of CD82 (CD82ΔC mutant) inhibits endocytic trafficking of the tetraspanin and compromises its activity toward heparin-binding EGF-activated EGFR. Reduced ubiquitylation of EGFR is accompanied by PKC-dependent increase in serine phosphorylation of c-Cbl in cells expressing elevated levels of CD82. Furthermore, phosphorylation of threonine 654 (PKC phosphorylation site) in the juxtamembrane domain of the receptor is considerably increased in CD82-expressing cells. These results describe previously unsuspected links between tetraspanin proteins and ubiquitylation of their molecular partners (e.g., EGFR). Our data identify CD82 as a new regulator of c-Cbl, which discriminatively controls the activity of this E3 ubiquitin ligase toward heparin-binding ligand-EGFR pairs. Taken together, these observations provide an important new insight into the modulatory role of CD82 in endocytic trafficking of EGF receptor."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m112.439380"xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/author"Berditchevski F."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/author"Raposo G."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/author"van Niel G."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/author"Mekada E."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/author"Iwamoto R."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/author"Odintsova E."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/author"Conjeaud H."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/pages"26323-26334"xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/title"Metastasis suppressor tetraspanin CD82/KAI1 regulates ubiquitylation of epidermal growth factor receptor."xsd:string
http://purl.uniprot.org/citations/23897813http://purl.uniprot.org/core/volume"288"xsd:string
http://purl.uniprot.org/citations/23897813http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23897813
http://purl.uniprot.org/citations/23897813http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23897813
http://purl.uniprot.org/uniprot/#_A0A068JD88-mappedCitation-23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23897813
http://purl.uniprot.org/uniprot/#_A8K2T7-mappedCitation-23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23897813
http://purl.uniprot.org/uniprot/#_A0A068JCC9-mappedCitation-23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23897813
http://purl.uniprot.org/uniprot/#_A0A1Y0B9F8-mappedCitation-23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23897813
http://purl.uniprot.org/uniprot/#_A0A1Y0B9F6-mappedCitation-23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23897813
http://purl.uniprot.org/uniprot/#_A0A1Y0B9G5-mappedCitation-23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23897813
http://purl.uniprot.org/uniprot/#_A0A1Y0B9F1-mappedCitation-23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23897813
http://purl.uniprot.org/uniprot/#_A0A1Y0B9G4-mappedCitation-23897813http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23897813