Heparin, Heparan Sulphate and the TGF-β Cytokine Superfamily
AbstractOf the circa 40 cytokines of the TGF-β superfamily, around a third are currently known to bind to heparin and heparan sulphate. This includes TGF-β1, TGF-β2, certain bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), as well as GDNF and two of its close homologues. Experimental studies of their heparin/HS binding sites reveal a diversity of locations around the shared cystine-knot protein fold. The activities of the TGF-β cytokines in controlling proliferation, differentiation and survival in a range of cell types are in part regulated by a number of specific, secreted BMP antagonist proteins. These vary in structure but seven belong to the CAN or DAN family, which shares the TGF-β type cystine-knot domain. Other antagonists are more distant members of the TGF-β superfamily. It is emerging that the majority, but not all, of the antagonists are also heparin binding proteins. Any future exploitation of the TGF-β cytokines in the therapy of chronic diseases will need to fully consider their interactions with glycosaminoglycans and the implications of this in terms of their bioavailability and biological activity. View Full-Text
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Rider, C.C.; Mulloy, B. Heparin, Heparan Sulphate and the TGF-β Cytokine Superfamily. Molecules 2017, 22, 713.
Rider CC, Mulloy B. Heparin, Heparan Sulphate and the TGF-β Cytokine Superfamily. Molecules. 2017; 22(5):713.Chicago/Turabian Style
Rider, Chris C.; Mulloy, Barbara. 2017. "Heparin, Heparan Sulphate and the TGF-β Cytokine Superfamily." Molecules 22, no. 5: 713.
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