RGD Reference Report - Phosphorylation of SNAP-23 by IkappaB kinase 2 regulates mast cell degranulation. - Rat Genome Database

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

Authors: Suzuki, K  Verma, IM 
Citation: Suzuki K and Verma IM, Cell. 2008 Aug 8;134(3):485-95. doi: 10.1016/j.cell.2008.05.050.
RGD ID: 8553272
Pubmed: PMID:18692471   (View Abstract at PubMed)
PMCID: PMC2586340   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2008.05.050   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:O703778553272PMID:18692471IntAct 
protein binding enablesIPIUniProtKB:Q9QY788553272PMID:18692471IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Ikbkb  (inhibitor of nuclear factor kappa B kinase subunit beta)
Snap23  (synaptosome associated protein 23)


Additional Information