Introduction
Cellular responses to external stimuli are coordinated by intracellular transducers, which rapidly relay a chemical signal from the cell membrane to specific effector sites inside the cell. The transducers are typically enzymes and adaptor proteins, such as kinases, phosphatases, lipases, and G-proteins, while the signal is frequently an allosteric activator such as Ca2+, cAMP, phospholipid, and phosphate. Response to external signals may occur in seconds, e.g. changes in ion channels and membrane structure, to minutes, e.g. trafficking of proteins to cell surface, to hours, e.g. changes in protein levels due to gene expression. The diversity and detail of these signalling pathways is both remarkable and only partly understood. The discovery of numerous proteins within decipherable biochemical pathways has provided novel approaches to controlling specific cell responses. For instance, the overexpression of multiple genes encoding inflammatory enzymes, cytokines, adhesion molecules, and proteases is responsible for diseases such as asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, inflammatory bowel disease psoriasis and colitis. By targeting key signalling components of these pathways for therapeutic intervention, it is believed that a new generation of drugs will attack the underlying cause of disease and not just the disease symptoms.
A sufficient description of all of the molecular drug targets available in cell signalling pathways is not possible within the confines of this chapter, when it is estimated that there are between 400 and 600 protein kinases alone encoded in the human genome.