PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling.
PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling.
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PTK 2B促进TBK 1和STING寡聚化并增强STING-TBK 1信号传导。
DOI：
10.1038/s41467-023-43419-4
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发表时间：
2023-11-21
影响因子：
16.6
通讯作者：
Sun, Qinmiao
中科院分区：
文献类型：
--
作者：
Lin, Yongfang;Yang, Jing;Yang, Qili;Zeng, Sha;Zhang, Jiayu;Zhu, Yuanxiang;Tong, Yuxin;Li, Lin;Tan, Weiqi;Chen, Dahua;Sun, Qinmiao
TANK结合激酶1（TBK1）是调节抗病毒天然免疫反应的关键激酶。虽然TBK1的寡聚化对其完全激活至关重要，但TBK1如何形成寡聚体的分子机制仍不清楚。在此，我们发现蛋白酪氨酸激酶2β（PTK2B）是一种与TBK1相互作用的蛋白，并调节TBK1的寡聚化。功能分析显示，在小鼠胚胎成纤维细胞、巨噬细胞和树突状细胞中，PTK2B缺失会减弱抗病毒信号传导，遗传学实验表明，Ptk2b基因缺陷型小鼠比对照小鼠更易受到病毒感染。从机制上讲，我们证明PTK2B直接磷酸化TBK1的Tyr591残基，从而增加TBK1的寡聚化和激活。此外，我们发现PTK2B还与干扰素基因刺激蛋白（STING）相互作用，并能以不依赖激酶的方式促进其寡聚化。总之，PTK2B通过不同机制增强TBK1和STING的寡聚化，进而调节STING - TBK1的激活，以确保有效的抗病毒天然免疫反应。
TBK1在抗病毒天然免疫反应中发挥核心作用。本文作者鉴定出PTK2B是一种与TBK1和STING寡聚化以及STING - TBK1信号激活相关的相互作用蛋白。
TANK-binding kinase 1 (TBK1) is a key kinase in regulating antiviral innate immune responses. While the oligomerization of TBK1 is critical for its full activation, the molecular mechanism of how TBK1 forms oligomers remains unclear. Here, we show that protein tyrosine kinase 2 beta (PTK2B) acts as a TBK1-interacting protein and regulates TBK1 oligomerization. Functional assays reveal that PTK2B depletion reduces antiviral signaling in mouse embryonic fibroblasts, macrophages and dendritic cells, and genetic experiments show that Ptk2b-deficient mice are more susceptible to viral infection than control mice. Mechanistically, we demonstrate that PTK2B directly phosphorylates residue Tyr591 of TBK1, which increases TBK1 oligomerization and activation. In addition, we find that PTK2B also interacts with the stimulator of interferon genes (STING) and can promote its oligomerization in a kinase-independent manner. Collectively, PTK2B enhances the oligomerization of TBK1 and STING via different mechanisms, subsequently regulating STING-TBK1 activation to ensure efficient antiviral innate immune responses. TBK1 plays a central role in the antiviral innate response. Here the authors identify PTK2B as an interacting protein linked to TBK1 and STING oligomerisation and the activation of STING-TBK1 signaling.
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影响因子：
14.9
作者：
Ma J;Chen T;Wu S;Yang C;Bai M;Shu K;Li K;Zhang G;Jin Z;He F;Hermjakob H;Zhu Y
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作者：
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