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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
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    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.
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