Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells
Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells
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DOI：
10.1038/ni.2685
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发表时间：
2013-09-01
影响因子：
30.5
通讯作者：
Batista, Facundo D.
中科院分区：
文献类型：
--
作者：
Castello, Angelo;Gaya, Mauro;Batista, Facundo D.
衔接子Nck将受体信号传导与细胞骨架调节联系起来。在此我们发现Nck还通过在B细胞活化后募集衔接子BCAP来控制磷脂酰肌醇-3-OH激酶（PI（3）K）-激酶Akt通路。Nck通过免疫球蛋白-a组分尾部204位的非免疫受体酪氨酸基活化基序（ITAM）磷酸化酪氨酸残基直接与B细胞抗原受体（BCR）结合。Nck的基因切除导致BCR信号传导缺陷，这导致体内B细胞的存活和增殖受到阻碍。事实上，Nck缺陷小鼠的抗体应答也受到相当大的损害。因此，我们证明了Nck在将BCAP募集到BCR信号传导位点从而调节B细胞中PI（3）K-Akt通路中的一种以前未知的衔接子功能。
The adaptor Nck links receptor signaling to cytoskeleton regulation. Here we found that Nck also controlled the phosphatidylinositol-3-OH kinase (PI(3)K)-kinase Akt pathway by recruiting the adaptor BCAP after activation of B cells. Nck bound directly to the B cell antigen receptor (BCR) via the non-immunoreceptor tyrosine-based activation motif (ITAM) phosphorylated tyrosine residue at position 204 in the tail of the immunoglobulin-a component. Genetic ablation of Nck resulted in defective BCR signaling, which led to hampered survival and proliferation of B cells in vivo. Indeed, antibody responses in Nck-deficient mice were also considerably impaired. Thus, we demonstrate a previously unknown adaptor function for Nck in recruiting BCAP to sites of BCR signaling and thereby modulating the PI(3) K-Akt pathway in B cells.