The adaptor protein 3BP2 associates with VAV guanine nucleotide exchange factors to regulate NFAT activation by the B-cell antigen receptor
The adaptor protein 3BP2 associates with VAV guanine nucleotide exchange factors to regulate NFAT activation by the B-cell antigen receptor
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DOI：
10.1182/blood-2003-08-2965
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发表时间：
2005-02-01
期刊：
影响因子：
20.3
通讯作者：
Deckert, M
中科院分区：
文献类型：
--
作者：
Foucault, I;Le Bras, S;Deckert, M
b细胞抗原受体（BCR）的参与激活Src和Syk家族的激酶以及由接头蛋白组装的信号复合物，这些激酶决定了b细胞的命运和功能。接头3BP2/SH3BP2是一种Abl Src同源结构域3 （SH3）结合和syk激酶相互作用蛋白，在T细胞、自然杀伤细胞（NK）和亲碱性细胞中表现出积极的调节作用。然而，它在BCR信号传导中的作用是完全未知的。在B淋巴瘤细胞上BCR聚集后，3BP2被酪氨酸磷酸化，3BP2是Syk和Fyn的底物，而不是Btk的底物。为了进一步探索31131132在B细胞中的功能，我们筛选了酵母2-杂交B淋巴细胞文库，发现3BP2是Vav蛋白的结合伙伴。3BP2和Vav蛋白之间的相互作用包括组成机制和诱导机制。3BP2还与BCR信号通路的其他组分相互作用，包括Syk和磷脂酶C γ (plc - γ)。此外，过表达和RNAi阻断实验表明，3BP2调节bcr介导的活化T细胞核因子（nfat）的活化。最后，有证据表明3BP2可以与Vav蛋白和Rho GTPases协同激活nfat。我们的研究结果表明3BP2可能通过Vav蛋白调控bcr介导的基因激活。(C) 2005年由美国血液病学会出版。
Engagement of the B-cell antigen receptor (BCR) activates kinases of the Src and Syk families and signaling complexes assembled by adaptor proteins, which dictate B-cell fate and function. The adaptor 3BP2/SH3BP2, an Abl Src homology domain 3 (SH3)-binding and Syk-kinases interacting protein, exhibits positive regulatory roles in T, natural killer (NK), and basophilic cells. However, its involvement in BCR signaling is completely unknown. Here we show that 3BP2 is tyrosine phosphorylated following BCR aggregation on B lymphoma cells, and that 3BP2 is a substrate for Syk and Fyn, but not Btk. To further explore the function of 31131132 in B cells, we screened a yeast 2-hybrid B-lymphocyte library and found 3BP2 as a binding partner of Vav proteins. The interaction between 3BP2 and Vav proteins involved both constitutive and inducible mechanisms. 3BP2 also interacted with other components of the BCR signaling pathway, including Syk and phospholipase C gamma (PLC-gamma). Furthermore, overexpression and RNAi blocking experiments showed that 3BP2 regulated BCR-mediated activation of nuclear factor of activated T cells (NFATs). Finally, evidence was provided that 3BP2 functionally cooperates with Vav proteins and Rho GTPases to activate NFATs. Our results show that 3BP2 may regulate BCR-mediated gene activation through Vav proteins. (C) 2005 by The American Society of Hematology.