Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells
Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells
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DOI：
10.1016/j.yexcr.2013.12.026
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发表时间：
2014-03-10
影响因子：
3.7
通讯作者：
Sada, Kiyonao
中科院分区：
文献类型：
--
作者：
Chihara, Kazuyasu;Kimura, Yukihiro;Sada, Kiyonao
衔接蛋白c-Abl SH 3结构域结合蛋白-2（3BP 2）已知在免疫受体介导的信号转导中起调节作用。我们先前已经证明小鼠3BP 2中Tyr（174）、Tyr（183）和TyP（446）主要被Syk磷酸化，并且小鼠3BP 2的Tyr（183）和Src同源2（SH 2）结构域的磷酸化对于B细胞受体（BCR）诱导的人B细胞中活化T细胞核因子（NFAT）的活化是关键的。在这份报告中，我们已经表明，Syk，而不是Abl家族的蛋白酪氨酸激酶，是至关重要的BCR介导的酪氨酸磷酸化的3BP 2在鸡DT 40细胞。突变分析表明，鸡3BP 2的Tyr（174）、Tyr（183）和Tyr（426）是Syk的主要磷酸化位点，3BP 2的SH 2结构域是酪氨酸磷酸化的关键。此外，Tyr（426）的磷酸化是与Vav 3的SH 2结构域的诱导性相互作用所必需的。此外，当与野生型的情况相比时，其中Tyr（426）被取代为Phe的3BP 2的突变形式的表达导致BCR介导的Rac 1活化的减少。总之，这些数据表明，3BP 2通过BCR刺激后Tyr（426）的Syk依赖性磷酸化调节Vav 3参与Rac 1的活化。(C)2014爱思唯尔公司All rights reserved.
Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr(174), Tyr(183) and TyP(446) in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr(183) and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr(174), Tyr(183) and Tyr(426) of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr(426) is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr(426) was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. (C) 2014 Elsevier Inc. All rights reserved.