The interaction of the transforming growth factor-βs with heparin/heparan sulfate is isoform-specific

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Abstract

We have undertaken a comparative study of the interaction of the three mammalian transforming growth factor-βs (TGF-β) with heparin and heparan sulfate. TGF-β1 and -β2, but not -β3, bind to heparin and the highly sulfated liver heparan sulfate. These polysaccharides potentiate the biological activity of TGF-β1 (but not the other isoforms), whereas a low sulfated mucosal heparan sulfate fails to do so. Potentiation is due to antagonism of the binding and inactivation of TGF-β1 by α2-macroglobulin, rather than by modulation of growth factor-receptor interactions. TGF-β2- α2-macroglobulin complexes are more refractory to heparin/heparan sulfate, and those involving TGF-β3 cannot be affected. Comparison of the amine acid sequences of the TGF-β isoforms strongly implicates the basic amine acid residue at position 26 of each monomer as being a vital binding determinant. A model is proposed in which polysaccharide binding occurs at two distinct sites on the TGF-β dimer. Interaction with heparin and liver heparan sulfate may be most effective because of the ability of the dimer to co-operatively engage two specific sulfated binding sequences, separated by a distance of approximately seven disaccharides, within the same chain.

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Lyon, M., Rushton, G., & Gallagher, J. T. (1997). The interaction of the transforming growth factor-βs with heparin/heparan sulfate is isoform-specific. Journal of Biological Chemistry, 272(29), 18000–18006. https://doi.org/10.1074/jbc.272.29.18000

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