A subcellular map of the human kinome
- Zhejiang University, China
- Yulin Normal University, China
- Peking University, China
- Goethe University Frankfurt, Germany
- Hangzhou Normal University, China
- First Affiliated Hospital of Zhengzhou University, China
Abstract
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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Images of KA were available at the Cell Image Library database (http://flagella.crbs.ucsd.edu/pages/kinome_atlas?token=dHqMbfi06S).
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The Kinome AtlasCell Image Library.
Article and author information
Author details
Funding
National Natural Science Foundation of China (31970726)
- Bin Zhao
National Natural Science Foundation of China (81730069)
- Bin Zhao
Ministry of Science and Technology of the People's Republic of China (2017YFA0504502)
- Bin Zhao
Natural Science Foundation of Zhejiang Province (LZ21C070002)
- Bin Zhao
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province
- Bin Zhao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jonathan A Cooper, Fred Hutchinson Cancer Research Center, United States
Version history
- Received: November 16, 2020
- Accepted: May 13, 2021
- Accepted Manuscript published: May 14, 2021 (version 1)
- Version of Record published: June 3, 2021 (version 2)
Copyright
© 2021, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A subcellular map of the human kinome
eLife 10:e64943.
https://doi.org/10.7554/eLife.64943
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