Cells in tissues need to be able to sense and interpret changes in their environment. For example, cells must be able to detect when they are in physical contact with other cells in order to regulate their growth and avoid the generation of tumors (“carcinogenesis”). In order to do so, cells place receptor molecules on their surface, often with a section of the receptor exposed to the outside of the cell (extracellular environment), and a section inside the cell (intracellular environment). These molecules are exposed to the environment outside of the cell and, therefore, in position to sense it. They are called receptors because when these come into contact with particular molecules (termed ligands), then chemical changes are induced to the receptor. These changes typically involve alterations in the three-dimensional shape of the receptor. These 3D structure changes affect both the extracellular and intracellular parts (domains) of the receptor. As a result, interaction of a receptor with its specific ligand which is located outside of the cell causes changes to the receptor part which is inside the cell. A signal from the extracellular space, therefore, can affect the biochemical state inside the cell.
Following receptor activation by the ligand, several steps can sequentially ensue. For example, the 3D shape changes to the intracellular domain may render it recognizable to catalytic proteins (enzymes) that are located inside the cell and have physical access to it. These enzymes may then induce chemical changes to the intracellular domain of the activated receptor, including the addition of phosphate chemical groups to specific components of the receptor (phosphorylation), or the physical separation (cleavage) of the intracellular domain. Such modifications may enable the intracellular domain to act as an enzyme itself, meaning that it may now catalyze the modification of other proteins in the cell. Enzymes which catalyze phosphorylation modifications are termed kinases. These modified proteins may then also be activated and enabled to induce further modifications to other proteins, and so on. This sequence of catalytic modifications is termed a “signal transduction pathway” or “second messenger cascade”. It is a critical mechanism employed by cells to sense their environment and induce complex changes to their state. Such changes may include, as noted, chemical modifications to other molecules, as well as decisions concerning which genes are activated and which are not (transcriptional regulation).
There are many signal transduction pathways in a cell and each of these involves many different proteins. This provides many opportunities for different signal transduction pathways to intercept (cross-talk). As a result, a cell simultaneously processes and interprets many different signals, as would be expected since the extracellular environment contains many different ligands. Cross-talk also allows the cell to integrate these many signals as opposed to process them independently. For example, mutually opposing signals may be activated at the same time by different ligands, and the cell can interpret these signals as a whole.
Signal transduction pathways are widely studied in biology as they provide mechanistic understanding of how a cell operates and takes critical decisions (e.g. to multiply, move, die, activate genes etc.). These pathways also provide many drug targets and are of great relevance to drug discovery efforts.