Visualizing Dynamics of Cell Signaling In Vivo with a Phase Separation-Based Kinase Reporter

Molecular Cell
Qiang ZhangXiaokun Shu

Abstract

Visualizing dynamics of kinase activity in living animals is essential for mechanistic understanding of cell and developmental biology. We describe GFP-based kinase reporters that phase-separate upon kinase activation via multivalent protein-protein interactions, forming intensively fluorescent droplets. Called SPARK (separation of phases-based activity reporter of kinase), these reporters have large dynamic range (fluorescence change), high brightness, fast kinetics, and are reversible. The SPARK-based protein kinase A (PKA) reporter reveals oscillatory dynamics of PKA activities upon G protein-coupled receptor activation. The SPARK-based extracellular signal-regulated kinase (ERK) reporter unveils transient dynamics of ERK activity during tracheal metamorphosis in live Drosophila. Because of intensive brightness and simple signal pattern, SPARKs allow easy examination of kinase signaling in living animals in a qualitative way. The modular design of SPARK will facilitate development of reporters of other kinases.

Citations

Jul 15, 2018·Chemistry : a European Journal·Hyeongjoo Choi, Yongwon Jung
Apr 30, 2019·Frontiers in Immunology·Stevan JeknićMarkus W Covert
Mar 24, 2020·Nature Structural & Molecular Biology·Xinye HanLei Zeng
Jul 15, 2020·Trends in Biochemical Sciences·Xin ZhouJin Zhang
Oct 15, 2018·Cell Systems·Rosa Martinez-CorralJordi Garcia-Ojalvo
Feb 16, 2021·Journal of Experimental Botany·Ying ChenHannes Vanhaeren
Apr 24, 2021·Journal of the American Chemical Society·Masaru YoshikawaShinya Tsukiji
Aug 3, 2021·Development·Akinobu NakamuraKazuhiro Aoki
Oct 23, 2020·Developmental Cell·Claire S SimonAnna-Katerina Hadjantonakis

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