Transforming growth factor‐β1 is a heparin‐binding protein: Identification of putative heparin‐binding regions and isolation of heparins with varying affinity for TGF‐β1
Journal of Cellular Physiology
Previous studies indicated that a major factor in heparin's ability to suppress the proliferation of vascular smooth muscle cells is an interaction with transforming growth factor‐β1 (TGF‐β1). Heparin appeared to bind directly to TGF‐β1 and to prevent the association of TGF‐β1 with α2‐macroglobulin (α2‐M). The present studies indicate that 20–70% of iodinated TGF‐β1 binds to heparin‐Sepharose and the retained fraction is eluted with ∼0.37 M NaCI. Native, unlabelled platelet TGF‐β1, however, is completely retained by heparin‐Sepharose and eluted with 0.9–1.2 M NaCI. Using synthetic peptides, the regions of TGF‐β1 that might be involved in the binding of heparin and other polyanions were examined. Sequence analysis of TGF‐β1 indicated three regions with a high concentration of basic residues. Two of these regions had the basic residues arranged in a pattern homologous to reported consensus heparin‐binding regions of other proteins. The third constituted a structurally novel pattern of basic residues. Synthetic peptides homologous to these three regions, but not to other regions of TGF‐β1, were found to bind to heparin‐Sepharose and were eluted with 0.15 M‐0.30 M NaCI. Only two of these regions were capable of blocking the binding of heparin to 125I‐TGF‐β. Immobilization of these peptides, followed by affinity purification of heparin, indicated that one peptide was capable of isolating subspecies of heparin with high and low affinity for authentic TGF‐β1. The ability of TGF‐β1 to bind to heparin or related proteoglycans under physiological conditions may be useful in understanding the biology of this pluripotent growth and metabolic signal. Conversely, a subspecies of heparin molecules with high affinity for TGF‐β1 may be a factor in some of the diverse biological actions of heparin. © 1992 Wiley‐Liss, Inc. Copyright © 1992 Wiley‐Liss, Inc.
McCaffrey, T., Falcone, D., & Du, B. (1992). Transforming growth factor‐β1 is a heparin‐binding protein: Identification of putative heparin‐binding regions and isolation of heparins with varying affinity for TGF‐β1. Journal of Cellular Physiology, 152 (2). http://dx.doi.org/10.1002/jcp.1041520226