Co-ligation of the antigen and Fc receptors gives rise to the selective modulation of intracellular signaling in B cells - Regulation of the association of phosphatidylinositol 3-kinase and inositol 5'-phosphatase with the antigen receptor complex
Co-ligation of the antigen and Fc receptors gives rise to the selective modulation of intracellular signaling in B cells - Regulation of the association of phosphatidylinositol 3-kinase and inositol 5'-phosphatase with the antigen receptor complex
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DOI：
10.1074/jbc.272.6.3838
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发表时间：
1997-02-07
影响因子：
4.8
通讯作者：
Diegel, ML
中科院分区：
文献类型：
--
作者：
Kiener, PA;Lioubin, MN;Diegel, ML
Fc受体（FcR）与B细胞表面免疫球蛋白（sIg）的交联可抑制细胞外钙离子的流入并消除增殖信号。在这份报告中，我们表明，共交联的FcR的抗原受体引起非常有选择性的调制信号转导的B细胞，共交联的sIg和FcR增强的FcR的磷酸化，衔接蛋白，Shc，和肌醇5 '-磷酸酶Ship。此外，FcR的磷酸化诱导其与Ship的结合，FcR和sig的交联降低了CD 19的酪氨酸磷酸化，从而导致磷脂酰肌醇3-激酶的结合减少。此外，73、39和34 kDa的其他几种蛋白质的磷酸化降低。用F（ab '）（2）或完整的抗IgG激活细胞诱导大多数其他蛋白质的酪氨酸磷酸化水平的非常相似的变化，并且没有观察到几种蛋白激酶的激活差异。这些结果表明，通过FcR传递的抑制信号不是由酪氨酸磷酸化的整体关闭介导的，而是，一种选择性机制，涉及衔接蛋白和酶Ship和磷脂酰肌醇3-激酶与抗原受体复合物相互作用的局部变化。
Cross-linking of the Fc receptor (FcR) to surface immunoglobulin (sIg) on B cells inhibits the influx of extracellular calcium and abrogates the proliferative signal, The mechanism by which this occurs is not well understood. In this report we show that co-cross-linking the FcR to the antigen receptor gives rise to very selective modulation of signal transduction in B cells, Co-cross-linking sIg and the FcR enhanced the phosphorylation of the FcR, the adapter protein, Shc, and the inositol 5'-phosphatase Ship. Furthermore, phosphorylation of the FcR induced its association with Ship, Cross-linking of the FcR and sig decreased the tyrosine phosphorylation of CD19, which led to a reduction in the association of phosphatidylinositol 3-kinasee. In addition, the phosphorylation of several other proteins of 73, 39, and 34 kDa was reduced, Activation of the cells with either F(ab')(2) or intact anti-IgG induced very similar changes in levels of tyrosine phosphorylation of most other proteins, and no differences in the activation of several protein kinases were observed, These results indicate that the inhibitory signal that is transmitted through the FcR is not mediated by a global shutdown of tyrosine phosphorylation but is, rather, a selective mechanism involving localized changes in the interactions of adapter proteins and the enzymes Ship and phosphatidylinositol 3-kinase with the antigen receptor complex.