| Information |
|---|
| myeloid differentiation primary response gene |
| InnateImmunity |
|
chr3 (+) (chr3:38155157-38159514) |
|
NM_002468
|
| 8 |
| 0 |
| 4 |
| 0 |
|
[ SNPper ]
[ GoldenPath ]
[ Gene Image ]
[ LocusLink ]
[ Omim ]
[ PubMed ]
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Of the two SNPs that passed through the genotyping and assay QC process, SNP MYD88_1296, at position 1296 relative to the codon start site, was monomorphic.
The remaining SNP, MYD88_4528, is reported under the genotyping results. Certain analysis are absent or should be interpreted accordingly given this single data point
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Because the TLRs [
1,
2,
3,
4,
5,
6,
7,
8,
9
] share sequence similarity with the IL-1R family in their cytoplasmic regions, it is not unexpected that downstream events are mediated by common components. MyD88 is an adaptor protein that links the IL-1 (α, β) receptor to IRAK, a serine-threonine kinase that is related to the Pelle kinase of Drosophila. Upon binding of ligand to IL-1R, IRAK is phosphorylated, subsequently dissociated from the receptor complex and associates with tumor necrosis factor receptor activated factor 6 (TRAF6). This process results in the activation of two different pathways that involve the c-Jun NH2-terminal kinase (Jnk) and p38 mitogen-activated protein kinase (MAPK) family and the Rel family transcription factor NF-kB. These pathways are evolutionally conserved. MyD88-/- mice do not respond to IL-1, IL-18, LPS or other microbial cell wall components, such as peptidoglycan and lipopeptides, which shows that this molecule is indispensable for responses to these stimuli. However, studies in MyD88-/- macrophages have suggested differences between TLR2 and TLR4 signaling. In MyD88-/- macrophages, production of inflammatory cytokines such as IL-1, TNF-alpha and IL-6 in response to LPS or mycoplasma lipopeptides is completely impaired. Mycoplasma-dependent activation of NF-kB and MAPK, which is mediated by TLR2, is completely abolished in both TLR2-/- and MyD88-/- macrophages. However, LPS activates NF-kB, Jnk or p38 in MyD88-/- macrophages, although this activation is delayed compared to wild-type macrophages. This suggests that there is a MyD88-independent pathway(s) that mediates NF-kB, Jnk or p38 activation after TLR4 signaling.
( See Omim for more ... ) |
