Initiation of a novel mode of membrane signaling: Vanadium facilitated signal transduction

As a first-row transition metal, vanadium can undergo numerous hydrolytic and chemical reactions in eukaryotic cells under physiological conditions. In model membrane systems, vanadium compounds interact with the lipid surfactants and either partially or fully penetrate the lipid interface. In eukaryotic cells, vanadium compounds interact with the plasma membrane lipid bilayer and drive signaling by three membrane proteins, identified to date, that function as receptors for physiologically important hormones. Perturbations in lipid order caused by vanadium compounds indirectly drive cell signaling by receptors that, in response to changes in lipid order, become concentrated in plasma membrane rafts. Importantly, this response occurs without binding of ligand to its receptor or direct interactions between receptor and vanadium compounds. We review here results reported for two tyrosine kinase receptors, the insulin receptor involved in regulating glucose uptake into cells and the Type I Fc epsilon receptors (Fc epsilon RI) involved in allergic responses. In addition, we examine the effects of vanadium compounds on a G protein-coupled receptor, the luteinizing hormone receptor (LHR), which is important in reproductive functions in both males and females. Together these observations document a novel mechanism of drug action that may be generalizable to other plasma membrane proteins using rafts to signal. (C) 2020 Elsevier B.V. All rights reserved.