Key result
This review summarizes the role of protein kinase G signaling in cardiac pathophysiology, its clinical targeting via phosphodiesterase inhibitors, and the proteomic challenges in studying it.
This review summarizes PKG signaling in cardiac pathophysiology, its clinical targeting, and the proteomic challenges in studying it for drug development.
PKG shows therapeutic potential in cardiac disease; leaves open proteomic validation before clinical translation.
The protective role of cyclic guanosine monophosphate (cGMP)-stimulated protein kinase G (PKG) in the heart makes it an attractive target for therapeutic drug development to treat a variety of cardiac diseases. Phosphodiesterases degrade cGMP, thus phosphodiesterase inhibitors that can increase PKG are of translational interest and the subject of ongoing human trials. PKG signaling is complex, however, and understanding its downstream phosphorylation targets and upstream regulation are necessary steps toward safe and efficacious drug development. Proteomic technologies have paved the way for assays that allow us to peer broadly into signaling minutia, including protein quantity changes and phosphorylation events. However, there are persistent challenges to the proteomic study of PKG, such as the impact of the expression of different PKG isoforms, changes in its localization within the cell, and alterations caused by oxidative stress. PKG signaling is also dependent upon sex and potentially the genetic and epigenetic background of the individual. Thus, the rigorous application of proteomics to the field will be necessary to address how these effectors can alter PKG signaling and interfere with pharmacological interventions. This review will summarize PKG signaling, how it is being targeted clinically, and the proteomic challenges and techniques that are being used to study it.
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Kirk et al. (2015) conducted a review in Cardiac diseases. Phosphodiesterase inhibitors targeting PKG signaling was evaluated. This review summarizes the role of protein kinase G signaling in cardiac pathophysiology, its clinical targeting via phosphodiesterase inhibitors, and the proteomic challenges in studying it.
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