Mimuro Hitomi, Berg Douglas E, Sasakawa Chihiro
Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Bioessays. 2008 Jun;30(6):515-20. doi: 10.1002/bies.20768.
Valuable insights into eukaryotic regulatory circuits can emerge from studying interactions of bacterial pathogens such as Helicobacter pylori with host tissues. H. pylori uses a type IV secretion system (T4SS) to deliver its CagA virulence protein to epithelial cells, where much of it becomes phosphorylated. CagA's phosphorylated and non-phosphorylated forms each interact with host regulatory proteins to alter cell structure and cell fate. Kwok and colleagues showed that CagA destined for phosphorylation is delivered using host integrin as receptor and H. pylori's CagL protein as an integrin-specific adhesin, and that CagL-integrin-binding activates the kinase cascade responsible for CagA phosphorylation. This research contributes to understanding infectious disease and the control of cell fates.
通过研究诸如幽门螺杆菌等细菌病原体与宿主组织的相互作用,可以深入了解真核生物的调控回路。幽门螺杆菌利用IV型分泌系统(T4SS)将其CagA毒力蛋白递送至上皮细胞,在那里大部分CagA会发生磷酸化。CagA的磷酸化形式和非磷酸化形式均与宿主调节蛋白相互作用,从而改变细胞结构和细胞命运。郭及其同事表明,注定要发生磷酸化的CagA是以宿主整合素作为受体、幽门螺杆菌的CagL蛋白作为整合素特异性粘附素来递送的,并且CagL与整合素的结合会激活负责CagA磷酸化的激酶级联反应。这项研究有助于理解传染病以及细胞命运的控制。