Cover image for Vol. 18 Issue 14

Editor: Meghan Campbell; Editorial Board Chairs: Thomas Carell, Donald Hilvert, Barbara Imperiali

Online ISSN: 1439-7633

Associated Title(s): ChemCatChem, ChemMedChem, ChemPhysChem, ChemSusChem

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July 14, 2017

Very Important Paper: Dissection of Kinase Isoforms through Orthogonal and Chemical Inducible Signaling Cascades

Siqi Zheng, Xinyuan Fan, Jie Wang, Jingyi Zhao, Peng R. Chen*

The interference from endogenous signaling enzymes represents a major hurdle for building an orthogonal signaling cascade inside cells, particularly among the close related isoforms within an enzyme family. Now, P.R. Chen (Beijing University, P.R. China) and co-workers employed a genetically-encoded chemical decaging strategy to build orthogonal-activated kinase isoforms with the endogenous counterparts temporally disabled by an extracellularly delivered bacterial effector. This approach eliminated any potential interference from the endogenous kinases, which allowed a specific, gain-of-function report of MEK1 activity (as opposed to MEK2) with high temporal resolution. This study differentiates the distinct enzymatic activity, feedback regulation, and signal outputs between these closely related kinase isoforms.

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