کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2037249 | 1072308 | 2008 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Phosphorylation of SNAP-23 by IκB Kinase 2 Regulates Mast Cell Degranulation Phosphorylation of SNAP-23 by IκB Kinase 2 Regulates Mast Cell Degranulation](/preview/png/2037249.png)
SummaryMast cells are known to play a pivotal role in allergic diseases. Cross-linking of the high-affinity receptor for IgE (FcɛRI) leads to degranulation and allergic inflammation; however, the regulatory mechanisms of IgE-dependent exocytosis remain unknown. We show here that IκB 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 FcɛRI 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.
Journal: - Volume 134, Issue 3, 8 August 2008, Pages 485–495