Genetically encoded fluorescent biosensors illuminate kinase signaling in cancer

被引:33
作者
Lin, Wei [1 ]
Mehta, Sohum [1 ]
Zhang, Jin [1 ]
机构
[1] Univ Calif San Diego, Dept Pharmacol, 9500 Gilman Dr, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
biosensor; fluorescence resonance energy transfer (FRET); phosphorylation; cancer; cell signaling; fluorescent protein; in vivo imaging; kinase signaling; posttranslational modification; HIPPO PATHWAY; PKA ACTIVITY; PROTEIN; PHOSPHORYLATION; VISUALIZATION; DYNAMICS; CALCIUM; CELLS; SRC; MUTATIONS;
D O I
10.1074/jbc.REV119.006177
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein kinase signaling networks stringently regulate cellular processes, such as proliferation, motility, and cell survival. These networks are also central to the evolution and progression of cancer. Accordingly, genetically encoded fluorescent biosensors capable of directly illuminating the spatiotemporal dynamics of kinase signaling in live cells are being increasingly used to investigate kinase signaling in cancer cells and tumor tissue sections. These biosensors enable visualization of biological processes and events directly in situ, preserving the native biological context and providing detailed insight into their localization and dynamics in cells. Herein, we first review common design strategies for kinase activity biosensors, including signaling targets, biosensor components, and fluorescent proteins involved. Subsequently, we discuss applications of biosensors to study the biology and management of cancer. These versatile molecular tools have been deployed to study oncogenic kinase signaling in living cells and image kinase activities in tumors or to decipher the mechanisms of anticancer drugs. We anticipate that the diversity and precision of genetically encoded biosensors will expand their use to further unravel the dysregulation of kinase signaling in cancer and the modes of actions of cancer-targeting drugs.
引用
收藏
页码:14814 / 14822
页数:9
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