The Role of Glycosylation in Receptor Signaling

Glycosylation is an important and highly regulated mechanism of secondary protein processing within cells. It plays a critical role in determining protein structure, function and stability. Structurally, glycosylation is known to affect the three dimensional configuration of proteins. This is of particular importance when considering protein-protein interactions such as those that occur between protein ligands and their cognate receptors or in the creation of other large macromolecular complexes. Many secreted proteins, such as hormones or cytokines, are glycosylated and this has been shown to impact in determining their activity when bound to receptors. Changes in these complexes result in alterations in how they recruit, interact and activate signaling proteins (e.g. G proteins). Additionally, signaling proteins are also glycosylated and this has distinct effects on their function. Ultimately, these effects help determine which signaling pathways are activated within the cell (Figure 1). Thus, glycosylation plays a key role in determining the cellular response to exogenous factors. This chapter will provide an overview of how glycosylation of ligands, their receptors, and signaling proteins affects signal transduction in mammalian cells by discussing specific examples of how receptor signaling is regulated by glycosylation.