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Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor.
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- Author(s): Brown KJ;Brown KJ; Parish CR
- Source:
Biochemistry [Biochemistry] 1994 Nov 22; Vol. 33 (46), pp. 13918-27.
- Publication Type:
Journal Article
- Language:
English
- Additional Information
- Source:
Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370623 Publication Model: Print Cited Medium: Print ISSN: 0006-2960 (Print) Linking ISSN: 00062960 NLM ISO Abbreviation: Biochemistry Subsets: MEDLINE
- Publication Information:
Original Publication: Washington, American Chemical Society.
- Subject Terms:
- Abstract:
Recent studies have shown that fibroblast growth factors (FGFs) need to interact with cell-surface heparan sulfate proteoglycans (HSPGs) in order to bind to and activate FGF receptors. In this paper, three major heparin-binding proteins, histidine-rich glycoprotein (HRG) and antithrombin III (ATIII), which are constitutively present at high concentrations in plasma, and platelet factor 4 (PF4), which is released locally at high concentrations by degranulating platelets, were tested for their ability to act as modulators of FGF activity by competing with the FGFs for cell-surface HSPGs. HRGs from both chicken and human, and human PF4, were demonstrated to compete with each other and with acidic FGF (aFGF) and basic FGF (bFGF) for binding to BALB/c 3T3 cell-surface HSPGs, whereas ATIII did not compete. Thus, HRG, PF4, aFGF, and bFGF all interact with the same HS chains on the 3T3 cell surface, either binding to the same or binding to adjacent saccharide sequences on the chains. In terms of their relative binding affinity for cell-surface HSPGs, the hierarchy was shown to be PF4 > or = bFGF > aFGF = cHRG > hHRG. HRG was also shown to significantly inhibit both FGF-stimulated and endogenous 3T3 cell DNA synthesis. HRG also binds to extracellular matrices (ECM), originating from bovine corneal endothelial cells, in a heparin-inhibitable manner. Indeed, both HRG and PF4, at physiological concentrations, were shown to effectively inhibit the binding of 125I-aFGF and 125I-bFGF to ECM. In addition, HRG was able to displace biologically active bFGF from the ECM. On the basis of these findings, it is proposed that HRG and PF4 may act as positive regulators of FGF activity by displacing FGF from the ECM or basement membrane and making FGF available to responsive cells. Alternatively, they could act as negative regulators by masking HSPGs on responsive cells and preventing FGF receptor activation.
- Accession Number:
0 (Glycoproteins)
0 (Heparan Sulfate Proteoglycans)
0 (Proteins)
0 (Proteoglycans)
0 (histidine-rich proteins)
103107-01-3 (Fibroblast Growth Factor 2)
104781-85-3 (Fibroblast Growth Factor 1)
37270-94-3 (Platelet Factor 4)
9000-94-6 (Antithrombin III)
9007-49-2 (DNA)
9050-30-0 (Heparitin Sulfate)
EC 3.2.1.- (Glycoside Hydrolases)
EC 3.2.1.- (heparanase)
EC 3.2.1.31 (Glucuronidase)
- Publication Date:
Date Created: 19941122 Date Completed: 19941221 Latest Revision: 20190613
- Publication Date:
20240829
- Accession Number:
10.1021/bi00250a047
- Accession Number:
7524669
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