How were signal transduction pathways discovered?

When guanosine triphosphate (GTP) was added to the rat liver cell membrane receptor in 1970, Martin Rodbell observed that glucagon was no longer bound to the receptor and that the G-protein was stimulated. This resulted in a significant increase in the cell's metabolism, leading to the conclusion that the G protein functions as a transducer, taking in glucose molecules and influencing the cell.

For this, he and Alfred G. Gilman shared the 1994 Nobel Prize in Physiology and Medicine.

Signal transduction pathways were discovered through a combination of experiments in cell biology, biochemistry, and molecular biology conducted throughout the 20th century. One key discovery was made in the early 20th century when researchers observed that the binding of a hormone to its receptor on a cell's surface could initiate a series of biochemical reactions inside the cell. Subsequent research, including studies on bacterial chemotaxis and the action of neurotransmitters, further elucidated the concept of signal transduction. The development of techniques such as radiolabeling, cell culture, and molecular cloning also contributed to the understanding of signal transduction pathways. Major breakthroughs came in the latter half of the 20th century with the discovery of key signaling molecules such as protein kinases, G proteins, and second messengers like cyclic AMP and calcium ions. These discoveries laid the foundation for our current understanding of how cells receive and respond to signals from their environment.