Inhibition of G Proteins by Antisense Drugs

Abstract

In a multicellular organism, cells communicate with each other mostly through the cell surface, which is represented by the plasma membrane with its lipids and proteins. A subset of the membrane proteins, i.e., receptors, are specialized to recognize and bind signalling molecules if arriving at sufficient concentrations at the cell surfaces. These signalling molecules, called receptor ligands, are either synthesized and secreted by other cells of the organism or taken up from the outside world. Ligands can be hormones, neurotransmitters, autacoids, growth factors, odorants, or physical signals, such as light. The binding of ligands to their cognate receptors leads to intracellular responses, e.g., changes in intracellular ion concentrations, de novo synthesis of proteins, or secretion of presynthesized proteins or transmitters. In many regulatory processes, the intracellular response is mediated by so-called second messengers, e.g., cyclic adenosine or guanosine monophosphate (cAMP or cGMP) or inositol 1,4,5-trisphosphate (IP₃), which are generated upon receptor activation as a consequence of the ligand signalling. The extracellular signalling components or ligands are called first messengers, and the membrane structures leading to second messenger generation are generally covered by the terms receptors, signal transducers (G proteins), and effectors.