Proteoglycans: from structural compounds to signaling molecules

Our knowledge of proteoglycan biology has significantly expanded over the past decade with the discovery of a host of new members of this multifunctional family leading to their present classification into three major categories: ( 1) small leucine-rich proteoglycans, 2) modular proteoglycans, and 3) cell-surface proteoglycans. In addition to being structural proteins, proteoglycans play a major role in signal transduction with regulatory functions in various cellular processes. Being mostly extracellular, they are upstream of many signaling cascades and are capable of affecting intracellular phosphorylation events and modulating distinct pathways, including those driven by bone morphogenetic protein/transforming growth factor superfamily members, receptor tyrosine kinases, the insulin-like growth factor-I receptor, and Toll-like receptors. Mechanistic insights into the molecular and cellular functions of proteoglycans have revealed both the sophistication of these regulatory proteins and the challenges that remain in uncovering the entirety of their biological functions. This review aims to summarize the multiple functions of proteoglycans with special emphasis on their intricate composition and the newly described signaling events in which these molecules play a key role.