丝裂原活化蛋白激酶(MAPK)通路是真核细胞适应环境变化的主要途径,在微生物的情况下,营养和荷尔蒙信号,在多细胞生物的情况下。这些结构上保守的途径中的许多缺陷与不同的人类癌症有关。这些信号级联通常始于位于质膜中的传感器,通过特定的蛋白激酶激活保守的三方MAPK模块。它们的目标磷酸化,也就是说,胞浆蛋白和/或转录因子,然后触发适当的细胞反应。在酿酒酵母和其他真菌的模型中,细胞壁完整性途径(CWI)已被广泛研究,其组分可作为具有临床和农业重要性的抗真菌药物的靶标.另一个众所周知的MAPK级联,高渗透压甘油(HOG)途径,需要应对渗透压。在过去的十年里,越来越明显的是,这种途径不是以线性自上而下的方式起作用,但受到内部反馈机制以及交叉途径相互作用的高度调节。Jiménez-Gutiérrez等人的工作。在这个问题上提供了一种优雅的方式来识别这些复杂网络中的新玩家。评论:https://doi.org/10.1111/febs.15288。
Mitogen-activated protein kinase (MAPK) pathways are a major means of eukaryotic cells to adapt to environmental changes, in the case of microorganisms, and to nutritional and hormonal signals, in the case of multicellular organisms. Numerous defects in such architecturally conserved pathways have been associated with different human cancers. These signaling cascades usually commence with sensors located in the plasma membrane, which through specific protein kinases activate a conserved tripartite MAPK module. Phosphorylation of their targets, that is, cytosolic proteins and/or transcription factors, then triggers the proper cellular response. In the model yeast Saccharomyces cerevisiae and other fungi, the cell wall integrity pathway (CWI) has been extensively studied and its components may serve as targets for antifungal drugs of clinical and agricultural importance. Another well-known MAPK cascade, the high osmolarity glycerol (HOG) pathway, is required to cope with osmotic stress. In the past decade, it has become increasingly evident that such pathways do not act in a linear top-down fashion, but are highly regulated by internal feedback mechanisms as well as by cross-pathway interactions. The work of Jiménez-Gutiérrez et al. in this issue provides an elegant way to identify new players in these complex networks. Comment on: https://doi.org/10.1111/febs.15288.