Figure 4.

Use of nitrobenzyl and coumarin caging groups in the control of cell signaling. (a) Organelle targeting DEACM-caged arachidonic acid and sphingosine derivatives are localized as expected: mitochondria (upper left), lysosome (upper right), plasma membrane (lower left), and endoplasmic reticulum (lower right). (b) A kinase is rendered inactive through caging of a catalytic site lysine with 7-hydroxycoumarin, blocking ATP binding until exposure to 365 nm irradiation. The active kinase then phosphorylates its downstream substrate. This was applied to MEK1 within the Ras/MAPK signaling pathway in developing zebrafish embryos. Hyperactivation of MEK1 induces embryo dorsalization leading to an elongation phenotype at 8 hours post fertilization. (c) LCK is rendered inactive through caging of its catalytic site until light irradiation with 375 nm activates the enzyme, which in turn activates ITAMs through phosphorylation. ZAP70 gets recruited by ITAMs and phosphorylated by LCK to activate downstream effector molecules and induce multiple signaling pathways. Adapted with permission from ref. [72] and [73], Copyright 2018, John Wiley and Sons and Copyright 2017, American Chemical Society, respectively.