Coupling cofactor--a novel regulatory component in G protein-mediated signalling?
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Updated: Oct 13, 2026

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
1Institute of Pharmacology, Vienna University, Austria.
Abstract:
The model for studying the mechanism of G protein-mediated signalling cannot account for the observation that high-affinity binding of agonists to many different receptors is not dissociated by the addition of high concentrations of guanine nucleotides. Using the cerebral A1-adenosine receptor as a model system, we have recently identified a component which is responsible for this phenomenon. This protein, termed the coupling cofactor, can be solubilized from brain membranes and chromatographically resolved from both the G proteins and the receptor. Following reconstitution into appropriate acceptor membranes, the coupling cofactor confers resistance of high-affinity agonist binding to guanine nucleotides. The coupling cofactor acts as a brake and limits receptor-dependent signal amplification; in addition, it is a candidate for participating in the higher level organization of receptors and G proteins in membranes and in the membrane-delimited cross-talk between individual receptors. Here, we present a working hypothesis on the possible biological roles of the coupling cofactor.
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