A subcellular map of the human kinome

eLife

Tingbo Liang¹  Haidong Li²  Jianhui Zhao³  Jia Feng⁴  Li Li⁵  Manuel Kaulich⁶  Liangyi Chen⁷  Liuju Li⁷  Qinghua Liao⁸  Mei Tang⁸  Yuan Si⁸  Chenliang Wang⁸  Shuaifeng Li⁸  Feifeng Zhu⁸  Zongping Xia⁸  Xiaolei Cao⁸  Guoxuan Zhong⁸  Fangwei Wang⁹  Huasong Lu⁹  Haitao Zhang⁹  Xin-Hua Feng⁹  Bin Zhao^1,10 

[1] Cancer Center, Zhejiang University, Hangzhou, China;Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;College of Biology and Pharmacy, Yulin Normal University, Yulin, China;Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;Department of Ophthalmology, The Children’s Hospital, School of Medicine, and National Clinical Research Center for Child Health, Zhejiang University, Hangzhou, China;Institute of Aging Research, Hangzhou Normal University, Hangzhou, China;Institute of Biochemistry II, Goethe University Frankfurt-Medical Faculty, University Hospital, Frankfurt, Germany;State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China;The MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China;The MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China;Cancer Center, Zhejiang University, Hangzhou, China;The MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China;Cancer Center, Zhejiang University, Hangzhou, China;Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;

关键词: kinome;    subcellular localization;    phase separation;    mitochondrial;    MOK;    Human;   

DOI  :  10.7554/eLife.64943

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY