Heparan sulphates as membrane receptors for the fibroblast growth factors.

Abstract

The complex polymeric structure of heparan sulphate contains intra-chain sequences of sulphated sugar residues that define active sites for the binding and activation of growth factors. The molecular mechanisms of recognition and activation are slowly being revealed at least in the case of the interaction of heparan sulphate with basic fibroblast growth factor. Current data indicate that relatively long but specific binding sequences in heparan sulphate may induce a conformational change in basic fibroblast growth factor exposing a site on the protein that is recognised by signal transducing receptors. Heparan sulphate may also subserve functions of dimerisation of basic fibroblast growth factor and facilitation of receptor transfer by a secondary interaction with the receptor itself. Various models for heparan sulphate mediated induction of mitogenesis by basic fibroblast growth factor have been proposed and there are suggestions that the core protein of plasma membrane heparan sulphate-proteoglycans may participate in the cell signalling process. The vital importance of heparan sulphate in controlling growth factor activities has opened up a new chapter in proteoglycan research and has brought proteoglycans into the mainstream of cell biology. Further investigation of their mode of action is likely to reveal new information on the control of cell growth and development in both embryonic and adult tissues and may suggest novel methods of controlling diseases such as cancer, atherosclerosis or fibrosis that are driven by abnormal expression of growth factors or their receptors.