ABSTRACT
The first 15 years, or so, brought the realization that there existed a G protein coupled signal transduction mechanism by which hormone receptors regulate adenylyl cyclases and the light receptor rhodopsin activates visual phosphodiesterase. Three G proteins, Gs, Gi and transducin (T) had been characterized as alphabetagamma heterotrimers, and Gsalpha-GTP and Talpha-GTP had been identified as the sigaling arms of Gs and T. These discoveries were made using classical biochemical approaches, and culminated in the purification of these G proteins. The second 15 years, or so, are the subject of the present review. This time coincided with the advent of powerful recombinant DNA techniques. Combined with the classical approaches, the field expanded the repertoire of G proteins from 3 to 16, discovered the superfamily of seven transmembrane G protein coupled receptors (GPCRs) -- which is not addressed in this article -- and uncovered an amazing repertoire of effector functions regulated not only by alphaGTP complexes but also by betagamma dimers. Emphasis is placed in presenting how the field developed with the hope of conveying why many of the new findings were made.
Subject(s)
GTP-Binding Protein alpha Subunits/history , GTP-Binding Protein beta Subunits/history , GTP-Binding Protein gamma Subunits/history , Signal Transduction , Animals , GTP-Binding Protein alpha Subunits, G12-G13/chemistry , GTP-Binding Protein alpha Subunits, G12-G13/history , GTP-Binding Protein alpha Subunits, G12-G13/metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/chemistry , GTP-Binding Protein alpha Subunits, Gi-Go/history , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , History, 20th Century , Hydrolysis , Isoenzymes/history , Isoenzymes/metabolism , Phosphatidylinositols/history , Phosphatidylinositols/metabolism , Phospholipase C beta , Type C Phospholipases/history , Type C Phospholipases/metabolismABSTRACT
The realization that there existed a G-protein coupled signal transduction mechanism developed gradually and was initially the result of an ill fated quest for uncovering the mechanism of action of insulin, followed by a refocused research in many laboratories, including mine, on how GTP acted to increase hormonal stimulation of adenylyl cyclase. Independent research into how light-activated rhodopsin triggers a response in photoreceptor cells of the retina and the attendant biochemical studies joined midway and, without the left hand knowing well what the right hand was doing, preceded classical G protein research in identifying the molecular players responsible for signal transduction by G proteins.
