Title: Oligomeric self-association of basic fibroblast growth factor in the absence of heparin-like glycosaminoglycans.
Authors: Davis, J C; Venkataraman, G; Shriver, Z; Raj, P A; Sasisekharan, R
Published In Biochem J, (1999 Aug 01)
Abstract: Basic fibroblast growth factor (FGF-2) represents a class of heparin-binding growth factors that are stored in the extracellular matrix attached to heparin-like glycosaminoglycans (HLGAGs). It has been proposed that cell surface HLGAGs have a central role in the biological activity of FGF-2, presumably by inducing dimers or oligomers of FGF-2 and leading to the dimerization or oligomerization of FGF receptor and hence signal transduction. We have previously proposed that FGF-2 possesses a natural tendency to self-associate to form FGF-2 dimers and oligomers; HLGAGs would enhance FGF-2 self-association. Here, through a combination of spectroscopic, chemical cross-linking and spectrometric techniques, we provide direct evidence for the self-association of FGF-2 in the absence of HLGAGs, defying the notion that HLGAGs induce FGF-2 oligomerization. Further, the addition of HLGAGs seems to enhance significantly the FGF-2 oligomerization process without affecting the relative percentages of FGF-2 dimers, trimers or oligomers. FGF-2 self-association is consistent with FGF-2's possessing biological activity both in the presence and in the absence of HLGAGs; this leads us to propose that FGF-2 self-association enables FGF-2 to signal both in the presence and in the absence of HLGAGs.
PubMed ID: 10417324
MeSH Terms: Biopolymers; Circular Dichroism; Cross-Linking Reagents; Fibroblast Growth Factor 2/chemistry; Fibroblast Growth Factor 2/genetics; Fibroblast Growth Factor 2/metabolism*; Glycosaminoglycans/metabolism*; Heparin/metabolism; Humans; Mass Spectrometry; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism