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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Paolini, Rossella Molfetta, Rosa Beitz, Laurie O. Zhang, Juan Scharenberg, Andrew M. Piccoli, Mario Frati, Luigi Siraganian, Reuben Santoni, Angela |
| Abstract | Engagement of the high affinity receptor for IgE (FcεRI) on mast cells and basophils results in FcεRI β and γ subunits ubiquitination by an as yet undefined mechanism. Here we show that, upon FcεRI engagement on RBL-2H3 cells Syk undergoes ubiquitination and Syk kinase activity is required for its own ubiquitination and that of FcεRI β and γ chains. This requirement was demonstrated by overexpression of Syk wild-type or its kinase-dead mutant in RBL cells or using an Syk-deficient RBL-derived cell line transfected with wild-type or a kinase inactive form of Syk. We also identify c-Cbl as the E3 ligase responsible for both Syk and receptor ubiquitination. Furthermore, we demonstrate that Syk controls tyrosine phosphorylation of Syk-associated Cbl induced after receptor engagement. These data suggest a mutual regulation between Syk and Cbl activities. Finally, we show that a selective inhibitor of proteasome degradation induces persistence of tyrosine-phosphorylated receptor complexes, of activated Syk, and of FcεRI-triggered degranulation. Our results provide a molecular mechanism for down-regulation of engaged receptor complexes by targeting ubiquitinated FcεRI and activated Syk to the proteasome for degradation. |
| Related Links | http://www.jbc.org/content/277/40/36940.abstract |
| Ending Page | 36947 |
| Starting Page | 36940 |
| Page Count | 8 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 40 |
| Volume Number | 277 |
| DOI | 10.1074/jbc.M204948200 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2002-10-04 |
| Access Restriction | Open |
| Subject Keyword | Protein-tyrosine kinase (PTK) T cell antigen receptor (TCR) B cell antigen receptor (BCR) High affinity immunoglobulin E receptor (FcεRI) Low affinity immunoglobulin G receptor (CD16) Immune receptor (IR) Ubiquitin (Ub) Goat anti-mouse IgG F(ab′)2 fragment (GAM) Phosphotyrosine (PY) Immune receptor tyrosine-based activation motif (ITAM) Src homology 2 (SH2) Ubiquitin carrier protein (E2) Ubiquitin-protein isopeptide ligase (E3) Monoclonal antibody (mAb) Antigen (Ag) Hemagglutinin (HA) Dinitrophenyl (DNP) Earle's modified Eagle's medium (EMEM) Human serum albumin (HSA) MECHANISMS OF SIGNAL TRANSDUCTION |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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