Negative regulation of FcϵRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b
| Autor: | Shinkou Kyo, Kiyonao Sada, Xiujuan Qu, S. M. Shahjahan Miah, Koichiro Maeno, Hirohei Yamamura |
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| Rok vydání: | 2004 |
| Předmět: |
Time Factors
Transcription Genetic MAP Kinase Kinase 4 Syk environment and public health Biochemistry chemistry.chemical_compound hemic and lymphatic diseases Mast Cells Proto-Oncogene Proteins c-cbl Phosphorylation Enzyme Precursors biology Kinase Intracellular Signaling Peptides and Proteins Degranulation Hematology Protein-Tyrosine Kinases beta-N-Acetylhexosaminidases I-kappa B Kinase Cell biology Ubiquitin ligase Protein Transport Mitogen-Activated Protein Kinases biological phenomena cell phenomena and immunity Signal transduction Signal Transduction Subcellular Fractions Ubiquitin-Protein Ligases Immunology Down-Regulation Protein Serine-Threonine Kinases Transfection Membrane Microdomains Ribonucleases Cell Line Tumor Animals Humans Syk Kinase Ligase activity Adaptor Proteins Signal Transducing Mitogen-Activated Protein Kinase Kinases Phospholipase C gamma Receptors IgE Ubiquitin JNK Mitogen-Activated Protein Kinases Tyrosine phosphorylation Cell Biology Lipid Metabolism Phosphoproteins Precipitin Tests Molecular biology Protein Structure Tertiary Rats enzymes and coenzymes (carbohydrates) Gene Expression Regulation chemistry Type C Phospholipases Mutation biology.protein Tyrosine Calcium Carrier Proteins |
| Zdroj: | Blood. 103:1779-1786 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Aggregation of the high-affinity immunoglobulin E (IgE) receptor (FcepsilonRI) on mast cells induces a number of biochemical events, including protein-tyrosine phosphorylation leading to degranulation and multiple cytokine gene transcription. Here, we have demonstrated that a second member of the Cbl family of ubiquitin-protein ligase Cbl-b translocates into the lipid raft after FcepsilonRI engagement. Overexpression of Cbl-b in the lipid raft inhibits FcepsilonRI-mediated degranulation and cytokine gene transcription through the distinct mechanism. A point mutation of Cys373 in the RING finger domain of Cbl-b abrogates the suppression of FcepsilonRI-mediated degranulation but not cytokine gene transcription. The antigen-induced tyrosine phosphorylation of FcepsilonRI, Syk, phospholipase C-gamma (PLC-gamma), activation of c-Jun N-terminal kinase (JNK), extracellular signal regulated kinase (ERK), inhibitor of nuclear factor kappaB kinase (IKK), and Ca++ influx were all suppressed in the cells overexpressing Cbl-b in the lipid raft. In particular, the expression amount of Gab2 protein and thereby its FcepsilonRI-mediated tyrosine phosphorylation were dramatically down-regulated by ubiquitin-protein ligase activity of Cbl-b. These results suggest that Cbl-b is a negative regulator of both Lyn-Syk-LAT and Gab2mediated complementary signaling pathways in FcepsilonRI-mediated mast cell activation. |
| Databáze: | OpenAIRE |
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