Abstract：
Many viral, protozoal, and fungal pathogens represent major human and animal health problems due to their great potential of causing infectious diseases. Research on these pathogens has contributed substantially to our current understanding of both microbial virulence determinants and host key factors during infection. Countless studies have also shed light on the molecular mechanisms of host-pathogen interactions that are employed by these microbes. For example, actin cytoskeletal dynamics play critical roles in effective adhesion, host cell entry, and intracellular movements of intruding pathogens. Cortactin is an eminent host cell protein that stimulates actin polymerization and signal transduction, and recently emerged as fundamental player during host-pathogen crosstalk. Here we review the important role of cortactin as major target for various prominent viral, protozoal and fungal pathogens in humans, and its role in human disease development and cancer progression. Most if not all of these important classes of pathogens have been reported to hijack cortactin during infection through mediating up- or downregulation of cortactin mRNA and protein expression as well as signaling. In particular, pathogen-induced changes in tyrosine and serine phosphorylation status of cortactin at its major phospho-sites (Y-421, Y-470, Y-486, S-113, S-298, S-405, and S-418) are addressed. As has been reported for various Gram-negative and Gram-positive bacteria, many pathogenic viruses, protozoa, and fungi also control these regulatory phospho-sites, for example, by activating kinases such as Src, PAK, ERK1/2, and PKD, which are known to phosphorylate cortactin. In addition, the recruitment of cortactin and its interaction partners, like the Arp2/3 complex and F-actin, to the contact sites between pathogens and host cells is highlighted, as this plays an important role in the infection process and internalization of several pathogens. However, there are also other ways in which the pathogens can exploit the function of cortactin for their needs, as the cortactin-mediated regulation of cellular processes is complex and involves numerous different interaction partners. Here, the current state of knowledge is summarized.
摘要：
许多病毒，原生动物,和真菌病原体代表了主要的人类和动物健康问题，因为它们具有引起传染病的巨大潜力。对这些病原体的研究大大有助于我们目前对感染期间微生物毒力决定因素和宿主关键因素的理解。无数的研究也揭示了这些微生物所采用的宿主-病原体相互作用的分子机制。例如,肌动蛋白细胞骨架动力学在有效粘附中起关键作用，宿主细胞进入，和侵入病原体的细胞内运动。Cortactin是一种杰出的宿主细胞蛋白，可刺激肌动蛋白聚合和信号转导，最近成为宿主-病原体串扰的基本参与者。在这里，我们回顾了皮质肌动蛋白作为各种突出病毒的主要靶标的重要作用，人类的原生动物和真菌病原体，以及它在人类疾病发展和癌症进展中的作用。据报道，大多数（如果不是全部）这些重要的病原体在感染期间通过介导cortactinmRNA和蛋白质表达以及信号传导的上调或下调来劫持cortactin。特别是,病原体诱导的皮质肌动蛋白在其主要磷酸位点（Y-421，Y-470，Y-486，S-113，S-298，S-405和S-418）的酪氨酸和丝氨酸磷酸化状态的变化。正如已经报道的各种革兰氏阴性和革兰氏阳性细菌，许多致病病毒，原生动物,真菌也控制着这些调节的磷酸化位点，例如,通过激活激酶如Src，PAK,ERK1/2和PKD,已知会磷酸化皮质肌动蛋白。此外,Cortactin及其互动伙伴的招募，像Arp2/3复合物和F-肌动蛋白，强调了病原体和宿主细胞之间的接触部位，因为这在几种病原体的感染过程和内化中起着重要作用。然而,病原体还可以通过其他方式利用cortactin的功能来满足他们的需求，因为cortactin介导的细胞过程调节是复杂的，并且涉及许多不同的相互作用伙伴。这里,总结了当前的知识状况。
