A subcellular map of the human kinome

  1. Haitao Zhang
  2. Xiaolei Cao
  3. Mei Tang
  4. Guoxuan Zhong
  5. Yuan Si
  6. Haidong Li
  7. Feifeng Zhu
  8. Qinghua Liao
  9. Liuju Li
  10. Jianhui Zhao
  11. Jia Feng
  12. Shuaifeng Li
  13. Chenliang Wang
  14. Manuel Kaulich
  15. Fangwei Wang
  16. Liangyi Chen
  17. Li Li
  18. Zongping Xia
  19. Tingbo Liang
  20. Huasong Lu
  21. Xin-Hua Feng
  22. Bin Zhao  Is a corresponding author
  1. Zhejiang University, China
  2. Yulin Normal University, China
  3. Peking University, China
  4. Goethe University Frankfurt, Germany
  5. Hangzhou Normal University, China
  6. 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).

The following data sets were generated

Article and author information

Author details

  1. Haitao Zhang

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaolei Cao

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Mei Tang

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Guoxuan Zhong

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yuan Si

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Haidong Li

    College of Biology and Pharmacy, Yulin Normal University, Yulin, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4427-7920
  7. Feifeng Zhu

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Qinghua Liao

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Liuju Li

    State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Jianhui Zhao

    Department of Hepatobiliary and Pancreatic Surgery, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Jia Feng

    Department of ophthalmology, The Children's Hospital, School of Medicine, and National Clinical Research Center for Child Health, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6742-484X
  12. Shuaifeng Li

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Chenliang Wang

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Manuel Kaulich

    Institute of Biochemistry II, Goethe University Frankfurt, Frankfurt am Main, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9528-8822
  15. Fangwei Wang

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5617-282X
  16. Liangyi Chen

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1270-7321
  17. Li Li

    Institute of Aging Research, Hangzhou Normal University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  18. Zongping Xia

    Translational Medicine Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  19. Tingbo Liang

    Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  20. Huasong Lu

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  21. Xin-Hua Feng

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  22. Bin Zhao

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    For correspondence
    binzhao@zju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1690-646X

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

  1. Jonathan A Cooper, Fred Hutchinson Cancer Research Center, United States

Publication history

  1. Received: November 16, 2020
  2. Accepted: May 13, 2021
  3. Accepted Manuscript published: May 14, 2021 (version 1)
  4. 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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  1. Haitao Zhang
  2. Xiaolei Cao
  3. Mei Tang
  4. Guoxuan Zhong
  5. Yuan Si
  6. Haidong Li
  7. Feifeng Zhu
  8. Qinghua Liao
  9. Liuju Li
  10. Jianhui Zhao
  11. Jia Feng
  12. Shuaifeng Li
  13. Chenliang Wang
  14. Manuel Kaulich
  15. Fangwei Wang
  16. Liangyi Chen
  17. Li Li
  18. Zongping Xia
  19. Tingbo Liang
  20. Huasong Lu
  21. Xin-Hua Feng
  22. Bin Zhao
(2021)
A subcellular map of the human kinome
eLife 10:e64943.
https://doi.org/10.7554/eLife.64943

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