A subcellular map of the human kinome.
A subcellular map of the human kinome.
复制标题
人类激酶组的亚细胞图谱
作者：
Zhang H;Cao X;Tang M;Zhong G;Si Y;Li H;Zhu F;Liao Q;Li L;Zhao J;Feng J;Li S;Wang C;Kaulich M;Wang F;Chen L;Li L;Xia Z;Liang T;Lu H;Feng XH;Zhao B
人类激酶组包含 538 个激酶，通过催化蛋白质磷酸化发挥重要功能。激酶组亚细胞分布的注释极大地促进了正常和疾病机制的研究。在这里，我们展示了激酶组图谱 (KA)，这是一个基于图像的激酶组图谱，注释有 10 个细胞区室。 456 个表位标记激酶（代表人类激酶组的 85%）在 HeLa 细胞中表达，并在类似条件下通过免疫荧光显微镜成像。 KA 揭示了激酶家族丰富的亚细胞定位，并在线粒体、质膜、细胞外空间和其他结构中发现了一系列新的激酶定位。此外，KA 证明了液-液相分离在激酶缩合物形成中的作用。 MOK 作为线粒体激酶的鉴定揭示了其在嵴动力学、呼吸和氧化应激反应中的功能。尽管由于过度表达或表位标记而可能出现错误定位，但该激酶组的亚细胞图谱可用于完善涉及蛋白质磷酸化的调节机制。
The human kinome comprises 538 kinases playing essential functions by catalyzing protein phosphorylation. Annotation of subcellular distribution of the kinome greatly facilitates investigation of normal and disease mechanisms. Here, we present Kinome Atlas (KA), an image-based map of the kinome annotated to 10 cellular compartments. 456 epitope-tagged kinases, representing 85% of the human kinome, were expressed in HeLa cells and imaged by immunofluorescent microscopy under a similar condition. KA revealed kinase family-enriched subcellular localizations and discovered a collection of new kinase localizations at mitochondria, plasma membrane, extracellular space, and other structures. Furthermore, KA demonstrated the role of liquid-liquid phase separation in formation of kinase condensates. Identification of MOK as a mitochondrial kinase revealed its function in cristae dynamics, respiration, and oxidative stress response. Although limited by possible mislocalization due to overexpression or epitope tagging, this subcellular map of the kinome can be used to refine regulatory mechanisms involving protein phosphorylation.