Fig 6. Orthogonal control of signal transduction systems by redox-sensing mechanisms.
The three major types of signal transduction systems for high-energy chemical signaling (illustrated for kinase signaling), redox signaling and ionic signaling, share common features of having proximal signal generators and distal signal response elements. In each case, the signal generators and response elements are proteins. In some cases, specific Cys residues are obligatory components of the signaling mechanism. These are termed “redox-signaling” Cys in the present article. In most cases, other non-obligatory Cys residues are present. Redox-sensitive Cys of this type are considered “redox-sensing” Cys in the present article. The concept of redox sensing is that covalent or non-covalent modification of these redox-sensing thiols provides means to alter protein activity, protein-protein interaction, translational diffusion and other characteristics which can govern amplitude of signals without fundamentally altering the signaling mechanism. Because cells undergo characteristic changes in redox potential through the life cycle, this means that kinase, redox and ionic signaling mechanisms can be “throttled” by appropriate redox-sensing thiols that respond to those thiol/disulfide redox changes in dividing, non-dividing and apoptotic cells. Similarly, because redox potentials are controlled differently in subcellular compartments, the same signaling mechanism can be differentially controlled by the prevailing local redox environment.