Modulatory Effects of Proteoglycans on Proteinase Activities

Abstract

Proteoglycans (PGs), composed of a core protein and one or more covalently attached sulfated glycosaminoglycan (GAG) chains, interact with a wide range of bioactive molecules, such as growth factors and chemokines, to regulate cell behaviors in normal and pathological processes. Additionally, PGs, through their compositional diversity, play a broad variety of roles as modulators of proteinase activities. Interactions of proteinases with other molecules on the plasma membrane anchor and activate them at a specific location on the cell surface. These interactions with macromolecules other than their own protein substrates or inhibitors result in changes in their activity and/or may have important biological effects. Thus, GAG chains induce conformational changes upon their binding to peptides or proteins. This behavior may be related to the ability of GAGs to act as modulators for some proteins (1) by acting as crucial structural elements by the control of proteinase activities, (2) by increasing the protein stability, (3) by permitting some binding to occur, exposing binding regions on the target protein, or (4) by acting as coreceptors for some inhibitors, playing important roles for the acceleration of proteinase inhibition. Understanding the modulatory effects exerted by PGs on proteinase activities is expected to lead to new insights in the understanding of some molecular systems present in pathological states, providing new targets for drug therapy.