Pleiotrophin interacts with glycosaminoglycans in a highly flexible and adaptable manner

Pleiotrophin (PTN) is a potent mitogenic cytokine whose activities are controlled by its interactions with glycosaminoglycan (GAG). We examined the specificity of PTN for several types of GAG oligosaccharides. Our data indicate that the interaction of PTN with GAGs is dependent on the sulfation density of GAGs. Surprisingly, an acidic peptide also had similar interactions with PTN as GAGs. This shows that the interaction of PTN with anionic polymers is flexible and adaptable and that the charge density is the main determinant of the interaction. In addition, we show that PTN can compensate for the loss of its termini in interactions with heparin oligosaccharides, allowing it to maintain its affinity for GAGs in the absence of the termini. Taken together, these data provide valuable insight into the interactions of PTN with its proteoglycan receptors.