Oligomeric self-association of basic fibroblast growth factor in the absence of heparin-like glycosaminoglycans.
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.
Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J C
JC
Davis
G
G
Venkataraman
Z
Z
Shriver
P A
PA
Raj
R
R
Sasisekharan
D001704:Biopolymers; D002942:Circular Dichroism; D003432:Cross-Linking Reagents; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D001704:Biopolymers; D003432:Cross-Linking Reagents; D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D006493:Heparin