Interaction of platelet factor 4 with fibroblast growth factor 2 is stabilised by heparan sulphate.
AffiliationPaterson Institute for Cancer Research, Manchester, UK.
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AbstractThe CXC chemokine platelet factor 4 (PF4) appears to inhibit tumour growth through its modulation of the activity of angiogenic growth factors. We investigated the heparan sulphate-dependent mechanism of PF4 inhibition of fibroblast growth factor 2 (FGF-2). The ability of PF4 to bind simultaneously to both FGF-2 and HS was assessed using affinity gel chromatography. Thirty-three to forty-two percent more HS bound to the FGF-2 affinity gel in the presence of PF4 than with HS alone. Protection assays showed that PF4 and FGF-2 bound to adjacent or overlapping sites together covering a 12 kDa stretch of HS. This study suggests that the three components may form a ternary complex. PF4 released at sites of angiogenesis may bind to angiogenic growth factors attached to endothelial cell surface HS to disrupt or prevent them from interacting with their signalling receptors. Manipulation of this mechanism may prove useful for clinical intervention of angiogenesis.
CitationInteraction of platelet factor 4 with fibroblast growth factor 2 is stabilised by heparan sulphate. 2003, 35 (7):1052-5 Int. J. Biochem. Cell Biol.
JournalThe International Journal of Biochemistry & Cell Biology
- Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor.
- Authors: Brown KJ, Parish CR
- Issue date: 1994 Nov 22
- Inhibitory effect of platelet factor 4 on human erythroleukemic cells is dependent on cell surface heparan sulfate.
- Authors: Maurer AM, Han ZC, Dhermy D, Briere J
- Issue date: 1996 Apr
- Interaction of heparan sulfate from mammary cells with acidic fibroblast growth factor (FGF) and basic FGF. Regulation of the activity of basic FGF by high and low affinity binding sites in heparan sulfate.
- Authors: Rahmoune H, Chen HL, Gallagher JT, Rudland PS, Fernig DG
- Issue date: 1998 Mar 27
- Interaction of fibroblast growth factor-1 and related peptides with heparan sulfate and its oligosaccharides.
- Authors: Fromm JR, Hileman RE, Weiler JM, Linhardt RJ
- Issue date: 1997 Oct 15
- Suppression by platelet factor 4 of the myogenic activity of basic fibroblast growth factor.
- Authors: Peng H, Wen TC, Igase K, Tanaka J, Matsuda S, Aburaya J, Sakanaka M
- Issue date: 1997 Jun