The signal transduction codes

Cells react to a wide variety of physical and chemical stimuli from the environment, and in general their reaction consists in the expression of specific genes. We need therefore to understand how the outside signals influence the genes, but for a long time all that could be said was that there must be a physical contact between them. The turning point, in this field, came with the discovery that external signals never reach the genes (Figure 4-8). They are invariably transformed into a different world of internal signals, called second messengers, and only these, or their derivatives, reach the genes. In most cases, the molecules of the external signals (known as first messengers) do not even enter the cell and are captured by specific receptors on the cell membrane, but even those which do enter (some hormones) must interact with intracellular receptors in order to act on genes (Sutherland, 1972).
The transfer of information from environment to genes takes place therefore in two distinct steps: one from first to second messengers, which is called signal transduction, and a second pathway from second messengers to genes which is known as signal integration.
The study of signal transduction turned out to be a veritable mine of surprises. There are literally hundreds of first messengers (hormones, growth factors, neurotransmitters, etc.) whereas the known second messengers are only four (cyclic AMP, calcium ions, inositol trisphosphate and diacylglycerol), as shown in Figure 4-9 (Alberts et al., 1994).
First and second messengers belong therefore to two independent worlds, which suggests immediately that signal transduction is likely to require the intervention of organic codes. But let us see if we can explain the experimental data in a different way.
It would be possible to manage without codes, for example, if every first messenger could set in motion a unique set of second messengers – as illustrated in Figure 4-10A – because in this case the signals would still be able to instruct the genes even without reaching them.
The facts, however, are very different. Acetylcholine, for example, is the signal that nerves deliver to most muscles, but does not have a unique meaning.