Phosphorylation-independent ubiquitylation and endocytosis of Fc gammaRIIA

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 t...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-11, Vol.281 (44), p.33242-33249
Main Authors: Mero, Patricia, Zhang, Christine Y, Huang, Zhen-Yu, Kim, Moo-Kyung, Schreiber, Alan D, Grinstein, Sergio, Booth, James W
Format: Article
Language:English
Subjects:
Adaptor Protein Complex 2 - metabolism
Antigens, CD - metabolism
Cell Line
Clathrin - metabolism
Endocytosis
Leupeptins - pharmacology
Mutation - genetics
Phosphorylation - drug effects
Proteasome Endopeptidase Complex - metabolism
Proteasome Inhibitors
Protein Binding
Receptors, IgG - metabolism
src-Family Kinases - metabolism
Ubiquitin - metabolism
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Summary: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.
ISSN:0021-9258