Protein–protein interactions define specificity in signal transduction

Virtually every aspect of cellular function within a metazoan organism, including proliferative status, metabolism, gene expression, cytoskeletal organization, and indeed the cell's very survival, is dependent on external signaling molecules, either in the form of soluble hormones or proteins anchored to the surface of an adjacent cell or the extracellular matrix (ECM). These factors exert their effects either by binding receptors displayed on the surface of the cell or, in the case of compounds such as steroids, by traversing the plasma membrane and directly engaging intracellular receptors. In addition, these external signals can be linked to intrinsic cues that regulate events such as polarity and asymmetric cell division, and that monitor the molecular composition of the cell, and therefore determine whether suitable conditions prevail for cell growth and division.

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. …