Hereditary and acquired defects in signaling through the hormone-receptor-G protein complex

Extracellular signals reach the interior of cells as second messengers through intermediary transducers located within or closely associated with the plasma membrane. One of the most common pathways involves the interaction of the extracellular signaling element with a membrane-bound receptor and guanine nucleotide-binding regulatory protein (G protein). Inherited and acquired defects that alter the function of the first messenger (hormone, neurotransmitter, autacoid, or paracrine substance) or either of the transducing components (G protein-coupled receptor or G protein) can lead to defective signaling and, ultimately, disease. Clinically relevant examples of defects of all three of those signaling components have recently been described. These can take the form of inherited or sporadic mutations of the genes encoding the various signaling components, or of neutralizing antibodies against those components. The purpose of this review is to summarize how acquired or inherited defects in each of those pathways might lead to diseases.