DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation.
DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation.
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DOI：
10.1038/ni.2305
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发表时间：
2012-05-13
影响因子：
30.5
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中科院分区：
文献类型：
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DOCK 8和MyD 88与血清学记忆有关。在这里，我们报告抗体反应受损和CD 27+记忆B细胞严重减少DOCK 8缺陷患者。Toll样受体9（TLR 9）-而不是CD 40-驱动的B细胞增殖和免疫球蛋白产生在DOCK 8缺陷的B细胞中严重减少。相反，TLR 9驱动的AICDA、CD 23和CD 86的表达以及NF-κB、p38和Rac 1的活化是完整的。DOCK 8与正常B细胞中的MyD 88和酪氨酸激酶Pyk 2组成性相关。在TLR 9连接后，DOCK 8被Pyk 2酪氨酸磷酸化，结合Src家族激酶林恩，并将TLR 9连接至TLR 9驱动的B细胞增殖和分化所必需的Src-Syk-STAT 3级联。因此，DOCK 8在B细胞中充当TLR 9-MyD 88信号传导途径中的衔接子。
DOCK8 and MyD88 have been implicated in serologic memory. Here we report antibody responses were impaired and CD27+ memory B cells were severely reduced in DOCK8-deficient patients. Toll-like receptor 9 (TLR9)- but not CD40-driven B cell proliferation and immunoglobulin production were severely reduced in DOCK8-deficient B cells. In contrast, TLR9-driven expression of AICDA, CD23 and CD86, and activation of NF-κB, p38 and Rac1 were intact. DOCK8 associated constitutively with MyD88 and the tyrosine kinase Pyk2 in normal B cells. Following TLR9 ligation, DOCK8 became tyrosine phosphorylated by Pyk2, bound the Src family kinase Lyn and linked TLR9 to a Src-Syk-STAT3 cascade essential for TLR9-driven B cell proliferation and differentiation. Thus, DOCK8 functions as an adaptor in a TLR9-MyD88 signaling pathway in B cells.