Protein-protein interactions define specificity in signal transduction

Over the last two decades, we have achieved considerable understanding of the mechanisms by which signals are conveyed from receptors at the plasma membrane to their targets in the cytoplasm and nucleus. At heart, this is a problem of molecular recognition. Hormones must bind selectively to their receptors and these in turn must interact with specific cytoplasmic targets. To understand signal transduction in a general sense, it is important to know whether different biochemical pathways use related molecular devices to control cellular behavior. To understand specificity in signaling, we need to know how receptors interact with particular targets and how the proteins of one pathway can be insulated from related signaling components. At the same time, it is important to learn how distinct signaling pathways communicate with one another, since the entire cell must ultimately function as a single unit whose different elements respond in an organized fashion to external signals. A cell in the body will be exposed to many different stimuli, which it must integrate into a coherent response. Furthermore, although a rather large fraction of genes within nucleated cells appear to function in the processes of signal transduction and cellular organization, it is still remarkable that only a few thousand gene products can control the sophisticated behaviors of many different cell types. This immediately suggests that signaling proteins must act in a combinatorial fashion, since there are insufficient proteins for each to have a single biological role. For example, there are billions of neurons in the human brain, each of which must project its axon to the appropriate target, let alone undertake the complex biochemical events associated with neurotransmission and synaptic plasticity. Clearly, the signaling molecules that function in the process of axon guidance must act in a combinatorial way to generate the extreme complexity of the human nervous system. Here we will address some of the underlying biochemical mechanisms through which specificity is generated during signal transduction, and pursue the means by which signaling molecules may act in combination to generate complex biological responses.