CD40 employs p38 MAP kinase in IgE isotype switching.

@article{Brady2001CD40EP,
  title={CD40 employs p38 MAP kinase in IgE isotype switching.},
  author={K J Brady and Stephen N. Fitzgerald and Sigurður Ingvarsson and Carl A. K. Borrebaeck and Paul N Moynagh},
  journal={Biochemical and biophysical research communications},
  year={2001},
  volume={289 1},
  pages={
          276-81
        }
}
IgE switching requires the prior induction of C epsilon germline transcripts which is mediated by the concerted binding of STAT-6 and NF kappa B to the C epsilon promoter. These transcription factors are regulated by IL-4 and CD40, respectively. However the latter can effect other signaling pathways and the present study explores the role of p38 MAPK in induction of C epsilon germline transcripts. CD40 and IL-4, both alone and in synergy, were initially shown to activate the C epsilon promoter… 

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References

SHOWING 1-10 OF 28 REFERENCES
CD40 cross-linking induces Ig epsilon germline transcripts in B cells via activation of NF-kappaB: synergy with IL-4 induction.
TLDR
It is reported in this study that treatment of mouse M12.4.1 B lymphoma cells with soluble CD40 ligand (CD40L)-CD8alpha fusion protein modestly induces the promoter for germline epsilon transcripts, and that this induction synergizes with IL-4.
p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes.
TLDR
Observations show that the p38 MAPK pathway is required for CD40-induced proliferation and that CD40 induces gene expression via both p38MAPK-dependent and -independent pathways.
Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B.
TLDR
The results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF- kappa B consensus sites.
The transcription factor B cell-specific activator protein (BSAP) enhances both IL-4- and CD40-mediated activation of the human epsilon germline promoter.
TLDR
Reporter assays showed that BSAP plays a role in both IL-4-dependent induction and CD40-mediated up-regulation of human epsilon germline transcription, which was abrogated in REH cells that express a BSAP polypeptide truncated in the trans-activation domain.
Cooperation of binding sites for STAT6 and NF kappa B/rel in the IL-4-induced up-regulation of the human IgE germline promoter.
TLDR
The available data suggest that the NF kappa B2 nucleoprotein complex may cooperate with DNA-bound STAT6 to achieve IL-4-dependent activation of the human IgE germline gene, and two additional cis-acting elements that interact with members of the NFKappa B/rel transcription factor family in an IL- 4-independent fashion are described.
Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted State6 gene
TLDR
Stat6-l- mice were deficient in IL-4-mediated functions including Th2 helper T-cell differentiation, expression of cell surface markers, and immunoglobulin class switching to IgE, indicating the lack of a non-redundant function in normal development.
Tumour-necrosis-factor-receptor-associated factor 6, NF-kappaB-inducing kinase and IkappaB kinases mediate IgE isotype switching in response to CD40.
TLDR
The results suggest that CD40 employs TRAF-6, which presumably recruits NIK, which in turn employs IKK-1/IKK-2 to activate NF-kappaB and the Cepsilon promoter, the prologue to IgE switching, which defines a crucially important pathway in the generation of allergic states.
Characterization of an interleukin 4 (IL-4) responsive region in the immunoglobulin heavy chain germline epsilon promoter: regulation by NF- IL-4, a C/EBP family member and NF-kappa B/p50
TLDR
DNA elements required for induction of transcription of the germline C epsilon genes by IL-4 are defined and it is demonstrated that a 46-bp segment (residing at -126/-79 relative to the first RNA initiation site) contains anIL-4 responsive region.
Structure and expression of germline epsilon transcripts in human B cells induced by interleukin 4 to switch to IgE production
TLDR
Results indicate that induction of human germline epsilon-RNA does not necessarily result in IgE synthesis, and that additional regulatory mechanisms are involved in class switching.
S region transcription per se promotes basal IgE class switch recombination but additional factors regulate the efficiency of the process.
TLDR
It is demonstrated for the first time that, for optimal efficiency, the process requires the presence of the intact I region and/or I region promoter in cis, implicating factors beyond transcription through the S region in the regulation of class switching.
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