Explicit formulation of different receptor-G-protein interactions and effector regulation.

• MOTIVATION: 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.

Keyword

Adaptation; Physiological/physiology

Binding Sites

Comparative Study

Computer Simulation

GTP-Binding Proteins/*chemistry/*metabolism

Models; Biological

Models; Chemical

Protein Binding

Protein Interaction Mapping/*methods

Receptors; G-Protein-Coupled/*chemistry/*metabolism

Research Support; Non-U.S. Gov't

Signal Transduction/physiology

Publication and Content Type

ref (subject category)

art (subject category)