Explicit formulation of different receptor-G-protein interactions and effector regulation.
BACKGROUND
G-protein-coupled receptors (GPCRs) can create different intracellular signals depending on which G-proteins they couple to and which intracellular signal-integrators, such as adenylyl cyclases, are expressed in the cell. One and the same GPCR can activate multiple G-protein species, generating signals, which either inhibit or amplify each other. Because of this complexity, extraction of mechanistic information from concentration-response curves is not straightforward.


RESULTS
To tackle this problem, I describe in this paper explicit equations for GPCR-interaction with two G-protein species by different possible mechanisms, and also an equation for the regulation of an effector enzyme by the activated G-proteins or their effectors. Arithmetic solutions to these equations are presented, which resulted in the equations being applicable in a spreadsheet program environment. These equations are useful in simulations to analyze results, to design experiments and to test hypotheses. Some examples of this are presented in this study.
Kukkonen
Jyrki P
JP
Department of Neuroscience, Unit of Physiology, Uppsala University, BMC, P.O. Box 572, SE-75123 Uppsala, Sweden. jyrki.kukkonen@fysiologi.uu.se
D000222:Adaptation, Physiological / Q000502:physiology; D001665:Binding Sites; D003198:Computer Simulation; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008956:Models, Chemical; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins