IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51270-4.html
   My bibliography  Save this article

Light-gated integrator for highlighting kinase activity in living cells

Author

Listed:
  • Wei Lin

    (University of California San Diego)

  • Abhishek Phatarphekar

    (University of California San Diego)

  • Yanghao Zhong

    (University of California San Diego
    California Institute of Technology)

  • Longwei Liu

    (University of Southern California)

  • Hyung-Bae Kwon

    (Johns Hopkins University School of Medicine)

  • William H. Gerwick

    (University of California San Diego)

  • Yingxiao Wang

    (University of Southern California)

  • Sohum Mehta

    (University of California San Diego)

  • Jin Zhang

    (University of California San Diego
    University of California San Diego
    University of California San Diego
    University of California San Diego)

Abstract

Protein kinases are key signaling nodes that regulate fundamental biological and disease processes. Illuminating kinase signaling from multiple angles can provide deeper insights into disease mechanisms and improve therapeutic targeting. While fluorescent biosensors are powerful tools for visualizing live-cell kinase activity dynamics in real time, new molecular tools are needed that enable recording of transient signaling activities for post hoc analysis and targeted manipulation. Here, we develop a light-gated kinase activity coupled transcriptional integrator (KINACT) that converts dynamic kinase signals into “permanent” fluorescent marks. KINACT enables robust monitoring of kinase activity across scales, accurately recording subcellular PKA activity, highlighting PKA activity distribution in 3D cultures, and identifying PKA activators and inhibitors in high-throughput screens. We further leverage the ability of KINACT to drive signaling effector expression to allow feedback manipulation of the balance of GαsR201C-induced PKA and ERK activation and dissect the mechanisms of oncogenic G protein signaling.

Suggested Citation

  • Wei Lin & Abhishek Phatarphekar & Yanghao Zhong & Longwei Liu & Hyung-Bae Kwon & William H. Gerwick & Yingxiao Wang & Sohum Mehta & Jin Zhang, 2024. "Light-gated integrator for highlighting kinase activity in living cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51270-4
    DOI: 10.1038/s41467-024-51270-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51270-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51270-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yonghoon Kwon & Sohum Mehta & Mary Clark & Geneva Walters & Yanghao Zhong & Ha Neul Lee & Roger K. Sunahara & Jin Zhang, 2022. "Non-canonical β-adrenergic activation of ERK at endosomes," Nature, Nature, vol. 611(7934), pages 173-179, November.
    2. Danielle L. Schmitt & Stephanie D. Curtis & Anne C. Lyons & Jin-fan Zhang & Mingyuan Chen & Catherine Y. He & Sohum Mehta & Reuben J. Shaw & Jin Zhang, 2022. "Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Jin Zhang & Christopher J. Hupfeld & Susan S. Taylor & Jerrold M. Olefsky & Roger Y. Tsien, 2005. "Insulin disrupts β-adrenergic signalling to protein kinase A in adipocytes," Nature, Nature, vol. 437(7058), pages 569-573, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yaqiong Li & Zhipeng Niu & Jichao Yang & Xuke Yang & Yukun Chen & Yingying Li & Xiaohan Liang & Jingwen Zhang & Fuqiang Fan & Ping Wu & Chao Peng & Bang Shen, 2023. "Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Yingfeng Tu & Qin Yang & Min Tang & Li Gao & Yuanhao Wang & Jiuqiang Wang & Zhe Liu & Xiaoyu Li & Lejiao Mao & Rui zhen Jia & Yuan Wang & Tie-shan Tang & Pinglong Xu & Yan Liu & Lunzhi Dai & Da Jia, 2024. "TBC1D23 mediates Golgi-specific LKB1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51270-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.