The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling.
The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling.
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DOI：
10.1084/jem.188.7.1333
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发表时间：
1998-10-05
期刊：
影响因子：
--
通讯作者：
Dumont DJ
中科院分区：
文献类型：
--
作者：
Liu Q;Oliveira-Dos-Santos AJ;Mariathasan S;Bouchard D;Jones J;Sarao R;Kozieradzki I;Ohashi PS;Penninger JM;Dumont DJ
Ship是Src同源2结构域，含有肌醇多磷酸5-磷酸酶，其被认为是造血细胞中的重要信号分子。在B细胞中，Ship与Fcγ受体II B（FcγRIIB）（免疫球蛋白（IG）G Fc部分的低亲和力受体）结合，并在B细胞抗原受体（BCR）-FcγRIIB共连接后迅速酪氨酸磷酸化。在由基因靶向Ship−/−胚胎干细胞产生的Ship−/−重组激活基因（Rag）−/−嵌合小鼠中研究了Ship在淋巴细胞中的功能。Ship−/−Rag−/−嵌合体显示B细胞数量减少，基础血清IG总体增加。Ship−/−脾B细胞对BCR-FcγRIIB共连接的反应表现出延长的Ca 2+内流、体外增殖增加和丝裂原活化蛋白激酶（MAPK）活化增强。这些结果表明，Ship在Fcγ RIIB介导的BCR信号转导抑制中起重要作用，并且Ship是Ca 2+通量和MAPK激活的关键负调节剂。
Ship is an Src homology 2 domain containing inositol polyphosphate 5-phosphatase which has been implicated as an important signaling molecule in hematopoietic cells. In B cells, Ship becomes associated with Fcγ receptor IIB (FcγRIIB), a low affinity receptor for the Fc portion of immunoglobulin (Ig)G, and is rapidly tyrosine phosphorylated upon B cell antigen receptor (BCR)–FcγRIIB coligation. The function of Ship in lymphocytes was investigated in Ship−/− recombination-activating gene (Rag)−/− chimeric mice generated from gene-targeted Ship−/− embryonic stem cells. Ship−/−Rag−/− chimeras showed reduced numbers of B cells and an overall increase in basal serum Ig. Ship−/− splenic B cells displayed prolonged Ca2+ influx, increased proliferation in vitro, and enhanced mitogen-activated protein kinase (MAPK) activation in response to BCR–FcγRIIB coligation. These results demonstrate that Ship plays an essential role in FcγRIIB-mediated inhibition of BCR signaling, and that Ship is a crucial negative regulator of Ca2+ flux and MAPK activation.
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