Coupling cofactor--a novel regulatory component in G protein-mediated signalling?
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.
Nanoff
C
C
Institute of Pharmacology, Vienna University, Austria.
Freissmuth
M
M
D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins