Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells

被引：54

作者：

Castello, Angelo ^{[1
]}

Gaya, Mauro ^{[1
]}

Tucholski, Johannes ^{[2
]}

Oellerich, Thomas ^{[3
]}

Lu, Kun-Hui ^{[4
]}

Tafuri, Anna ^{[4
]}

Pawson, Tony ^{[5
,6
]}

Wienands, Juergen ^{[2
]}

Engelke, Michael ^{[2
]}

Batista, Facundo D. ^{[1
]}

机构：

[1] London Res Inst Canc Res UK, Lymphocyte Interact Lab, London, England

[2] Univ Gottingen, Inst Cellular & Mol Immunol, D-37073 Gottingen, Germany

[3] Goethe Univ Frankfurt, Dept Med 2, D-60054 Frankfurt, Germany

[4] German Canc Res Ctr, Dept Mol Immunol, Heidelberg, Germany

[5] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada

[6] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 09期

关键词：

NON-ITAM TYROSINE; ANTIGEN RECEPTOR; LINKER PROTEIN; ACTIVATION; BLNK; PROLIFERATION; EXPRESSION; REQUIRES; ALPHA; GRB2;

D O I：

10.1038/ni.2685

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：966 / +

页数：13

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