Regulation of G-protein-mediated signal transfer by ions

Abstract

Receptor-mediated activation of guanine nucleotide binding proteins (G-proteins) is profoundly modified by both mono- and divalent cations. Several divalent cations increase the affinity of many G-protein-coupled receptors for agonists at concentrations in the millimolar range. Micromolar concentrations of Mg2+ are required for receptor-mediated activation of G-proteins. Using the formyl peptide receptor of human leukemia (HL 60) as a model system, we have recently been able to demonstrate that two independent metal binding sites are present on the receptor-G-protein complex to mediate these two effects. We propose that the site that binds divalent cations in the millimolar range is contained in an extracellular domain of the receptor, whereas the site for micromolar Mg2+ is located on the G-protein. Sodium ions decrease the agonist affinity of many G-protein-coupled receptors and modify the interaction of G-proteins with guanine nucleotides. We suggest that sodium ions elicit these effects by interacting with a unique binding site present in an intracellular domain of either the receptor or some associated protein that is different from the G-protein.