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http://purl.uniprot.org/citations/14531861http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14531861http://www.w3.org/2000/01/rdf-schema#comment"

Background

Recent studies have demonstrated that c-Cbl functions as a ubiquitin-protein ligase toward immune receptors and non-receptor protein-tyrosine kinase Syk by facilitating their ubiquitination and subsequent targeting to proteasomes. However, it was not clear whether Src family kinase Lyn is regulated by the Cbl family of ubiquitin-protein ligases.

Results

Aggregation of the high affinity IgE receptor (Fc epsilon RI) induces the rapid ubiquitination of Lyn in rat basophilic leukaemia RBL-2H3 cells. Treatment of cells with a proteasome inhibitor enhances the ubiquitination of Lyn. Stimulation of Fc epsilon RI results in the association of Lyn with c-Cbl and Cbl-b, both of which then become tyrosine phosphorylated. Co-transfection study shows that both c-Cbl and Cbl-b could induce the ubiquitination of activated Lyn in COS cells. Furthermore, over-expression of membrane-anchored form of c-Cbl inhibits the Fc epsilon RI-mediated degranulation and cytokine gene production in RBL-2H3 cells by the down-regulation of the kinase activity of Lyn through the enhanced ubiquitination.

Conclusions

These results demonstrate that Lyn is down-regulated by c-Cbl-mediated ubiquitination and subsequent degradation in proteasome after Fc epsilon RI stimulation in mast cells. Targeting of c-Cbl in the lipid raft results in the inhibition of Fc epsilon RI-mediated mast cell activation."xsd:string
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http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/author"Kawauchi-Kamata K."xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/author"Kyo S."xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/author"Maeno K."xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/author"Miah S.M."xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/author"Qu X."xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/author"Sada K."xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/author"Yamamura H."xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/name"Genes Cells"xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/pages"825-836"xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/title"Negative regulation of Lyn protein-tyrosine kinase by c-Cbl ubiquitin-protein ligase in Fc epsilon RI-mediated mast cell activation."xsd:string
http://purl.uniprot.org/citations/14531861http://purl.uniprot.org/core/volume"8"xsd:string
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