Any one of a group of proteins that relay signals in mammalian cells (see signal transduction). They occur on the inner surface of the plasma membrane and transmit signals from receptors on the outer surface of the cell to intracellular components. G proteins are activated by binding to GTP and become inactive when they bind GDP (see guanosine). Large G proteins comprise three dissimilar subunits (denoted α, β, and γ: i.e. they are heterotrimeric); about 20 such proteins are known, associating with various types of cell surface receptors and transmitting signals to different intracellular pathways. A conformational change in the receptor caused by binding of its ligand enables the G protein to bind to the intracellular part of the receptor. This displaces the molecule of GDP from the G protein and allows GTP to take its place, thereby activating the G protein. The subunits dissociate and interact with other cellular components to trigger the signal pathways. Immediate targets of activated G proteins include adenylate cyclase and phospholipase C, which give rise to the second messengers cyclic AMP, inositol trisphosphate (IP3), and raised intracellular calcium ions. The α subunit has intrinsic GTPase activity and subsequently hydrolyses the GTP to GDP, permitting reassociation of the subunits and restoring the G protein to its inactive state. Small G proteins comprise a single polypeptide; the best characterized is RAS protein. The cholera toxin exerts its effects by changing the G protein in the epithelial cells of the intestine so that it is continually activated, which causes an abnormal increase in cellular adenylate cyclase levels. One consequence of this is that sodium ions are actively pumped into the intestine, causing water to follow by osmosis: the result is diarrhoea and dehydration.