Tyrosine kinase 2 interacts with the proapoptotic protein Siva-1 and augments its apoptotic functions.
Tyrosine kinase 2 interacts with the proapoptotic protein Siva-1 and augments its apoptotic functions.
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DOI：
10.1016/j.bbrc.2010.08.051
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发表时间：
2010-09
影响因子：
3.1
通讯作者：
H. Shimoda;K. Shide;T. Kameda;T. Matsunaga;K. Shimoda
中科院分区：
文献类型：
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作者：
H. Shimoda;K. Shide;T. Kameda;T. Matsunaga;K. Shimoda
Siva-1是一种具有诱导外源性（受体介导）和内源性（非受体介导）细胞凋亡潜力的分子。Siva-1与肿瘤坏死因子受体（TNFR）家族成员CD27、abl相关基因（ARG）和BCL-XL结合，据报道，这些伙伴分子增强了Siva-1的凋亡特性。在这项研究中，我们发现Siva-1也与Jak家族蛋白激酶的成员酪氨酸激酶2 （Tyk2）相互作用。Siva-1通过其n端区域与Tyk2结合，Tyk2使Siva-1在酪氨酸53和162位点磷酸化。在小鼠pro-B细胞、Ba/F3细胞中，Tyk2的表达增强了siva -1诱导的细胞凋亡。无论Siva-1是否磷酸化，Siva-1诱导的细胞凋亡的增强都得以保留，但Tyk2-Siva-1关联的消除几乎完全阻止了这种增强。这些结果表明，Siva-1和Tyk2之间的相互作用直接增强了Siva-1的凋亡活性。我们的新观察表明，Siva-1与Tyk2形成功能复合物，并参与抑制B淋巴细胞生长的信号转导。
Siva-1 is a molecule that has the potential to induce both extrinsic (receptor-mediated) and intrinsic (non-receptor-mediated) apoptosis. Siva-1 binds to CD27, a member of the tumor necrosis factor receptor (TNFR) family, Abl-related gene (ARG), and BCL-XL, and these partner molecules reportedly enhance the apoptotic properties of Siva-1. In this study, we show that Siva-1 also interacts with a member of the Jak family protein kinases, tyrosine kinase 2 (Tyk2). Siva-1 bound to Tyk2 via its N-terminal region, and Tyk2 phosphorylated Siva-1 at tyrosines 53 and 162. In murine pro-B cells, Ba/F3 cells, expression of Tyk2 augmented Siva-1-induced apoptosis. This augmentation of Siva-1-induced apoptosis was retained regardless of the phosphorylation of Siva-1, but was almost completely prevented by the abrogation of the Tyk2-Siva-1 association. These findings indicate that the interaction between Siva-1 and Tyk2 directly augments the apoptotic activity of Siva-1. Our novel observations suggest that Siva-1 forms a functional complex with Tyk2 and participates in the transduction of signals that inhibit B lymphocyte growth.