炭疽毒素的摄取与功能
中文名称
通路描述
炭疽芽孢杆菌通过分泌三种细菌蛋白（左位素/致死因子LF、细胞因子/水肿因子EF、保护素PA）在感染人类细胞中发挥作用。LF是一种蛋白酶，可切割并失活多种MAP2K（MAP激酶激酶）蛋白，从而破坏MAP激酶信号通路。EF是一种腺苷酸环化酶，介导cAMP的持续产生，而cAMP通常仅在细胞外信号作用下短暂且受严格调控地生成。LF和EF均依赖PA进入靶细胞，这是一种细菌双毒素策略。PA结合靶细胞受体，被furin或其他细胞蛋白酶切割，随后形成寡聚体，暴露出LF和EF分子的结合位点。该复合物通过氯酪蛋白介导的内吞作用进入靶细胞，并被递送至内体。内体的低pH导致细菌毒素复合物重排：PA寡聚体在内体膜上形成孔道，使LF和EF分子进入靶细胞细胞质。
英文描述
Drug-mediated inhibition of MET activation MET receptor tyrosine kinase (RTK) is a proto-oncogene that is frequently aberrantly activated in cancer through gene amplification and/or activating mutations that result in hypersensitivity to HGF stimulation or HGF-independent activation. Oncogenic MET activation can occur as a primary mechanism of malignant transformation or be selected secondarily, as a mechanism of resistance to therapeutics that target related RTKs, such as EGFR. MET targeted anti-cancer therapeutics, either recombinant monoclonal antibodies (MAbs) or small tyrosine kinase inhibitors (TKIs), have shown promise as a first-line agents for the treatment of solid tumors with primary MET activation or as second-line agents for the treatment of solid tumors with acquired MET-mediated resistance to other RTK-targeted therapies (reviewed in Comoglio et al. 2018).
所含基因
2 个基因