Redox Control Of Receptor Activation

Over the years, the sensitivity of ligand-receptor interactions to redox reagents has been demonstrated for most 7TMR systems. The roles of 7TMR and G protein cysteines have been extensively investigated using redox reagents and SDM, both alone and in combination. Ligand interactions with and activations of 7TMRs are sensitive to mild oxidation (generally beneficial) and reducing agents (generally destructive), as well as divalent metal ions and other typical cysteine-reactive entities. Conversely, G proteins are sensitive to NEM and reducing agents promote their activity. Interpretations from the use of redox reagents have always been unequivocal, both because of the different redox dosage sensitivities of the various components and because of the intricate feedback of, say, G protein release that downregulates receptor affinity and invites phosphorylation and internalization of the receptor. Anything that compromises one of the components may affect the performance of the others, directly or indirectly.

The ligand and G protein exist in different redox environments and communicate via a receptor that samples both environments. Are the confusing effects of redox reagents caused by different cellular backgrounds or do they reflect the microenvironment within the receptor? Substantial published evidence supports the role of the receptor, with its flexibility, as the mediator of redox-mediated signaling, and here are a few examples — some old and some new.

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