Hatakeyama Masanori
Division of Microbiology, Graduate School of Medicine, University of Tokyo.
Nihon Rinsho. 2012 Oct;70(10):1699-704.
Helicobacter pylori CagA is the first identified bacterial oncoprotein playing a critical role in gastric carcinogenesis. Upon delivery into gastric epithelial cells via type IV secretion, CagA is localized to the plasma membrane, where it acts as a pathogenic scaffold/hub that promiscuously interacts with a number of host signaling molecules. Especially, CagA binds to the polarity-regulating kinase PAR1/MARK and inhibits the kinase activity. Following tyrosine phosphorylation by host kinases, CagA also acquires the ability to interact with the oncogenic tyrosine phosphatase SHP2 and deregulates the phosphatase activity. Through these interactions, CagA deregulates intracellular signaling pathways involved in cell proliferation and cell movement, while causing epithelial junctional and polarity defects. These CagA activities collectively contribute to the development of gastric carcinoma.
幽门螺杆菌细胞毒素相关基因A（CagA）是首个被鉴定出的在胃癌发生过程中起关键作用的细菌癌蛋白。通过IV型分泌系统进入胃上皮细胞后，CagA定位于质膜，在那里它作为一个致病支架/枢纽，与许多宿主信号分子发生杂乱的相互作用。特别是，CagA与极性调节激酶PAR1/MARK结合并抑制其激酶活性。在被宿主激酶酪氨酸磷酸化后，CagA还获得了与致癌性酪氨酸磷酸酶SHP2相互作用的能力，并使磷酸酶活性失调。通过这些相互作用，CagA使参与细胞增殖和细胞运动的细胞内信号通路失调，同时导致上皮连接和极性缺陷。这些CagA的活性共同促成了胃癌的发展。
