Phosphorylation-independent Ubiquitylation and Endocytosis of FcγRIIA
| Autor: | Alan D. Schreiber, Moo-Kyung Kim, Zhen-Yu Huang, Patricia Mero, Sergio Grinstein, Christine Y. Zhang, James W. Booth |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Proteasome Endopeptidase Complex
Leupeptins media_common.quotation_subject Adaptor Protein Complex 2 Fc receptor Endocytosis Biochemistry Clathrin Cell Line Antigens CD Src family kinase Phosphorylation Internalization Receptor Molecular Biology media_common biology Ubiquitin Chemistry Receptors IgG Signal transducing adaptor protein Cell Biology Cell biology src-Family Kinases Mutation biology.protein Proteasome Inhibitors Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 281:33242-33249 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m605372200 |
| Popis: | Endocytosis of the Fc receptor Fc gammaRIIA depends on a functional ubiquitin conjugation system, and the receptor becomes ubiquitylated upon ligand binding. Phosphorylation of tyrosines in Fc gammaRIIA by Src family kinases is thought to be the initiating event in its signaling. However, although the Src family kinase inhibitor PP1 inhibited both ligand-induced phosphorylation of Fc gammaRIIA and phagocytosis in ts20 cells expressing Fc gammaRIIA, it did not inhibit receptor ubiquitylation or endocytosis of soluble ligands. Conversely, genistein and the proteasomal inhibitor MG132 did not inhibit receptor phosphorylation but strongly inhibited both receptor ubiquitylation and endocytosis. A region of the receptor lying within the immunoreceptor tyrosine-based activation motif was found to be necessary for both ubiquitylation and endocytosis. Ubiquitylation occurs at the plasma membrane before internalization. Endocytosis of Fc gammaRIIA is dependent on clathrin but independent of the adaptor protein AP-2. These findings point to a novel mechanism for ubiquitylation and endocytosis of this immunoreceptor. |
| Databáze: | OpenAIRE |
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