Phosphorylation of SNAP-23 by IkappaB kinase 2 regulates mast cell degranulation

Cell. 2008 Aug 8;134(3):485-95. doi: 10.1016/j.cell.2008.05.050.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Snap23 protein, mouse
  • Immunoglobulin E
  • I-kappa B Kinase