然后将这9个氨基酸一一突变为丙氨酸（Alanine），发现这些突变的确影响TBK1结合，尤其是L374A 点突变会让STING彻底失去活性。更进一步的IFN-β 荧光素酶报告分析证实这些突变影响干扰素的表达。Westernblot和免疫共沉淀也证实这些突变影响cGAS-STING通路的激活。

2025年3月18日 · Deletion of TBC1D23, a recently reported tethering factor, in mice impairs the STING-IFN-I signaling, but with insignificant effect on STING-NF-κB signaling. Mechanistically, TBC1D23 interacts ...

2023年1月12日 · Using a suite of genetic and pharmacological tools across multiple experimental model systems, we confirm a role for TBK1 as an immune-evasion gene. Targeting TBK1 enhances responses to PD-1...

2023年11月21日 · These DNA sensors then recruit a stimulator of IFN genes (STING) 9, subsequently activating TBK1/IKKi and the IKK complex to induce antiviral responses 10,11. TBK1 is one critical kinase in the...

在天然免疫系统中，TBK1以TLR依赖的方式介导I型IFN (IFN-α/β)和抗病毒天然免疫的诱导。 病毒dsRNA和TLR3的结合招募TRIF和TRAF3 ， 最后激活TBK1，TBK1与 NF-κB 激活激酶相关蛋白1 (NAP1)和IKKε形成复合物。 活化的TBK1磷酸化 IRF3，引起其同源二聚体化并易位到细胞核，从而驱动抗病毒I型IFN的表达。 当细胞感知入侵的病原体LPS时，它们也可以以TLR4依赖的方式介导IRF3磷酸化，从而诱导I型IFN的释放。 除TLRs外，病毒RNA激活的胞浆RIG-1样受体 …

TANK 结合激酶 1 （TBK1）通常被认为是先天免疫的激活剂，调节IFN-I、 NF-kB 和肿瘤坏死因子TNF诱导的 RIPK1依赖性细胞死亡 （RCD） 【2,3】。 TBK1的基因变异与 家族性肌萎缩侧索硬化症 （ALS）和额颞痴呆（FTD）相关。 在小鼠中，TBK1的 双等位基因 缺失在胚胎期是致命的，但对存活率没有影响。

2020年9月29日 · TANK-binding kinase 1 (TBK1), an IKK-related serine/threonine kinase, is pivotal for the induction of antiviral type I interferon (IFN) by TLR and RLR signaling pathways. In a previous study, we demonstrated that TBK1 spliced isoforms (TBK1_tv1 and TBK1_tv2) from zebrafish were dominant negative regulators in the RLR antiviral pathway by ...

2020年7月10日 · TANK-binding kinase 1 (TBK1), along with its close analogue I-kappa-B kinase epsilon, is a central kinase in innate adaptor complexes linking activation of PRRs to mobilization of transcriptional factors that transcribe proinflammatory cytokines, type I interferon (IFN-α/β), and myriads interferon stimulated genes.

TANK-binding kinase (TBK1) is an important signaling hub downstream of RLRs and DSRs. TBK1 activates IRF3 and IRF7, leading to IFN-I production and subsequent induction of interferon stimulated genes (ISGs). The objective of this study was to explore the potential of BX795, an inhibitor of TBK1, to downregulate IFN-I activation in pSS, SLE and SSc.

2012年3月6日 · Here, we showed that STING stimulates phosphorylation of IRF3 by the kinase TBK1 (TANK-binding kinase 1) in an in vitro reconstitution system. With this system, we identified a carboxyl-terminal region of STING that was both necessary and sufficient to activate TBK1 and stimulate the phosphorylation of IRF3.