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PMID:18692471
| Citation |
Suzuki, K and Verma, IM (2008) Phosphorylation of SNAP-23 by IkappaB kinase 2 regulates mast cell degranulation. Cell 134:485-95 |
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| Abstract |
Mast cells are known to play a pivotal role in allergic diseases. Cross-linking of the high-affinity receptor for IgE (FcepsilonRI) leads to degranulation and allergic inflammation; however, the regulatory mechanisms of IgE-dependent exocytosis remain unknown. We show here that IkappaB kinase (IKK) 2 in mast cells plays critical roles in IgE-mediated anaphylaxis in vivo, and IgE-mediated degranulation in vitro, in an NF-kB-independent manner. Upon FcvarepsilonRI stimulation, IKK2 phosphorylates SNAP-23, the target membrane soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor (SNARE), and ectopic expression of a phospho-mimetic mutant of SNAP-23 partially rescued the impaired IgE-mediated degranulation in IKK2-deficient mast cells. These results suggest that IKK2 phosphorylation of SNAP-23 leads to degranulation and anaphylactic reactions. While this reaction is NF-kB-independent, we additionally show that IKK2 also regulates late-phase allergic reactions promoted by the release of proinflammatory cytokines in an NF-kB-dependent manner. The findings suggest that IKK2 is a central player in allergic reactions. |
| Links |
PubMed PMC2586340 Online version:10.1016/j.cell.2008.05.050 |
| Keywords |
Anaphylaxis/immunology; Animals; Cell Degranulation; I-kappa B Kinase/metabolism; Immunoglobulin E/immunology; Mast Cells/cytology; Mast Cells/immunology; Mice; Phosphorylation; Qb-SNARE Proteins/metabolism; Qc-SNARE Proteins/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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