Signal Transduction - History

History

In 1970, Martin Rodbell examined the effects of glucagon on a rat's liver cell membrane receptor. He noted that guanosine triphosphate disassociated glucagon from this receptor and stimulated the G-protein, which strongly influenced the cell's metabolism. Thus he deduced that the G-protein was a transducer that accepted glucagon molecules and affected the cell. For this he shared the 1994 Nobel Prize in Physiology or Medicine with Alfred G. Gilman.

The earliest MEDLINE entry for "signal transduction" dates from 1972. Some early articles used the terms signal transmission and sensory transduction. In 1977, a total of 48,377 scientific papers -- including 11,211 e review papers -- were published on the subject. The term first appeared in a paper's title in 1979.Widespread use of the term has been traced to a 1980 review article by Rodbell: Research papers focusing on signal transduction first appeared in large numbers in the late 1980s and early 1990s.

Signal transduction involves the binding of extracellular signalling molecules and ligands to cell-surface receptors that trigger events inside the cell. The combination of messenger with receptor causes a change in the conformation of the receptor, known as receptor activation. This activation is always the initial step (the cause) leading to the cell's ultimate responses (effect) to the messenger. Despite the myriad of these ultimate responses, they are all directly due to changes in particular cell proteins. Intracellular signaling cascades can be started through cell-substratum interactions; examples are the integrin that binds ligands in the extracellular matrix and steroids. Most steroid hormones have receptors within the cytoplasm and act by stimulating the binding of their receptors to the promoter region of steroid-responsive genes. Examples of signaling molecules include the hormone melatonin, the neurotransmitter acetylcholine and the cytokine interferon γ.

The classifications of signalling molecules do not take into account the molecular nature of each class member; neurotransmitters range in size from small molecules such as dopamine to neuropeptides such as endorphins. Some molecules may fit into more than one class; for example, epinephrine is a neurotransmitter when secreted by the central nervous system and a hormone when secreted by the adrenal medulla.