G Protein Signaling

Since the initial discovery of the G protein-coupled receptor system that regulates cyclicAMP production the G protein field has rapidly expanded. Cell surface receptors that couple to heterotrimeric G proteins the G prote- coupled receptors (GPCRs) number in the hundreds and bind to a wide div- sity of ligands including biogenic amines (e. g. adrenaline) lipid derivatives (e. g. lysophosphatidic acid) peptides (e. g. opioid peptides) proteins (e. g. thyroid-stimulating hormone) and odorants to name a few. The GPCR system is found throughout biology in such simple organisms as yeast and in such more complex organisms as Dictyostelium discoideum (slime mold) Caen- habditis elegans (nematode worm) and of course in humans. GPCRs and their associated G protein systems are the subject of intense academic research and because of their involvement in a human biology and disease the pharmac- tical industry has large research initiatives dedicated to the study of GPCRs. By some estimates more than 50% of the pharmaceuticals on the market are targeted at GPCRs. The G protein/G protein-coupled receptor system consists of a receptor (GPCR) a heterotrimeric G protein consisting of ? ? and ? subunits and an effector. G protein effector molecules such as enzymes or ion channels respond to acti- tion by the G protein to generate second messengers or changes in membrane potential that lead to alterations in cell physiology.