Expansion of signal transduction by G proteins. The second 15 years or so: from 3 to 16 alpha subunits plus betagamma dimers.
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.
Birnbaumer
Lutz
L
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA. birnbau1@niehs.nih.gov
D000818:Animals; D044385:GTP-Binding Protein alpha Subunits / Q000266:history*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000737:chemistry / Q000266:history / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry / Q000266:history / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000266:history*; D044388:GTP-Binding Protein gamma Subunits / Q000266:history*; D049673:History, 20th Century; D006868:Hydrolysis; D007527:Isoenzymes / Q000266:history / Q000378:metabolism; D010716:Phosphatidylinositols / Q000266:history / Q000378:metabolism; D054799:Phospholipase C beta; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000266:history / Q000378:metabolism
C118981:G-protein Beta gamma; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D007527:Isoenzymes; D010716:Phosphatidylinositols; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D019206:GTP-Binding Protein alpha Subunits, Gi-Go