Rohde J R, Cardenas M E
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Curr Top Microbiol Immunol. 2004;279:53-72. doi: 10.1007/978-3-642-18930-2_4.
The TOR kinases were first identified in Saccharomyces cerevisiae as the targets of the immunosuppressive drug rapamycin. Subsequent studies employing rapamycin as a tool in yeast have given us insight into the structure and function of the TOR kinases, as well as the biological role of the TOR signaling program in transmitting nutrient signals to promote cell growth. One of the major advances from this area has been in defining an unexpected role for TOR signaling in the regulation of transcription. The identification of target genes subject to regulation by TOR has provided a platform for the dissection of the signaling events downstream of the TOR kinases. Studies aimed at understanding TOR-regulated transcription have begun to shed light on how TOR signaling cooperates with other signaling programs. In addition, the TOR pathway regulates the developmental program of pseudohyphal differentiation in concert with highly conserved MAP kinase and PKA signaling programs. Remarkably, rapamycin also blocks filamentation in a number of important human and plant pathogens and the mechanism of rapamycin action is conserved in Candida albicans and Cryptococcus neoformans. The antimicrobial properties of less immunosuppressive analogs of rapamycin hold promise for the development of an effective antifungal therapy.
TOR激酶最初在酿酒酵母中被鉴定为免疫抑制药物雷帕霉素的作用靶点。随后，在酵母中使用雷帕霉素作为工具进行的研究，让我们深入了解了TOR激酶的结构和功能，以及TOR信号通路在传递营养信号以促进细胞生长方面的生物学作用。该领域的一项重大进展是确定了TOR信号在转录调控中的意外作用。对受TOR调控的靶基因的鉴定，为剖析TOR激酶下游的信号事件提供了一个平台。旨在理解TOR调控转录的研究，已开始揭示TOR信号如何与其他信号通路协同作用。此外，TOR通路与高度保守的丝裂原活化蛋白激酶（MAP激酶）和蛋白激酶A（PKA）信号通路协同调节假菌丝分化的发育程序。值得注意的是，雷帕霉素还能阻断许多重要的人类和植物病原体的菌丝形成，并且雷帕霉素的作用机制在白色念珠菌和新型隐球菌中是保守的。雷帕霉素免疫抑制性较低的类似物的抗菌特性，为开发有效的抗真菌疗法带来了希望。
