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首页> 外文期刊>Biochemistry >Tyrosine Phosphorylation of Adaptor Protein 3BP2 Induces T Cell Receptor-Mediated Activation of Transcription Factor
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Tyrosine Phosphorylation of Adaptor Protein 3BP2 Induces T Cell Receptor-Mediated Activation of Transcription Factor

机译：衔接蛋白3BP2酪氨酸磷酸化诱导T细胞受体介导的转录因子激活。

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摘要

Molecular adaptors/scaffolds have indispensable roles in the activation of lymphocytes.In this report,we have demonstrated the role of tyrosine phosphorylation of an adaptor protein 3BP2(c-Abl-SH3 domain binding protein-2,also known as SH3BP2)in T cell receptor(TCR)-mediated activation of transcription factor.Short interfering RNA for 3BP2 suppresses the expression level of endogenous 3BP2 and inhibits TCR-mediated activation of interleukin(IL)-2 promoter and nuclear factor of activated T cells(NFAT)element.Engagement of TCR induces tyrosine phosphorylation and lipid raft translocation of 3BP2.The overexpression studies reveal that substitution of 3BP2-Tyr~183,Tyr~446,or Arg~486 in the SH2 domain suppresses TCR-mediated activation of NFAT.Point mutations of 3BP2 cannot affect the translocation of 3BP2 into the lipid raft.Phosphorylation of Tyr~183 is required for the interaction with Vavl,the guanine nucleotide exchanging factor of Racl.In fact,overexpression of dominant-negative form of Racl inhibits TCR-mediated activation of NFAT.Phosphorylation of Tyr~446 recruits the SH2 domain of Lck for the optimal activation of transcription factors.Furthermore,point mutation of Arg~486 in the 3BP2-SH2 domain that couples ZAP-70 to LAT dramatically reduces NFAT activation.These results suggest that the site-directed functions of 3BP2 induce the activation of transcription factors.
机译：分子衔接子/支架在淋巴细胞活化中起着不可或缺的作用。在本报告中，我们证明了酪氨酸磷酸化衔接蛋白3BP2（c-Abl-SH3结构域结合蛋白-2，也称为SH3BP2）在T细胞中的作用。受体（TCR）介导的转录因子激活.3BP2的短干扰RNA抑制内源性3BP2的表达水平，并抑制TCR介导的白介素（IL）-2启动子和活化T细胞（NFAT）元件的核因子的激活。过度表达研究表明，SH2结构域中3BP2-Tyr〜183，Tyr〜446或Arg〜486的取代可抑制TCR介导的NFAT活化，而3BP2的点突变无法抑制3BP2的酪氨酸磷酸化和脂质筏移位。 Tyr〜183的磷酸化是与Racl的鸟嘌呤核苷酸交换因子Vavl相互作用所必需的。事实上，显性负性形式的过表达Racl抑制了TCR介导的NFAT激活。Tyr〜446的磷酸化募集了Lck的SH2结构域，以最佳激活转录因子。此外，在ZBP-70与LAT偶联的3BP2-SH2结构域中，Arg〜486的点突变。这些结果表明3BP2的定点功能诱导了转录因子的激活。

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