Identification of a binding site on human FGF-2 for fibrinogen

Hu Peng, Abha Sahni, Philip Fay, Stephen Bellum, Igor Prudovsky, Thomas Maciag, Charles W. Francis

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Endothelial cell adhesive interactions are mediated by both fibrinogen and fibrin, and growth is stimulated by fibroblast growth factor 2 (FGF-2). We have shown previously that FGF-2 binds specifically and with high affinity to fibrinogen and fibrin and that fibrinogen potentiates the proliferative capacity of FGF-2 and also protects it from proteolytic degradation. To further characterize this interaction we have performed FGF-2 mutagenesis to identify the interactive site. Because FGF-1 has a similar structure to FGF-2 but does not bind to fibrinogen, we used a strategy of cassette and site-directed mutagenesis, exchanging residues from FGF-1 and FGF-2 and correlating structural changes with fibrinogen binding. Two cassette interchange mutants, 2212 and 2211, contained either the third cassette or both the third and fourth cassettes from FGF-1, and neither exhibited any affinity for fibrinogen. Exchange of 5 residues (Phe95, Ser100, Asn102, Arg107, and Arg109) from FGF-2 into the corresponding sites in the third cassette of FGF-1 imparted high-affinity binding with apparent dissociation constants (Kd) of 5.3 nM and 8.6 nM, respectively, compared with 1.3 nM for wild-type FGF-2. We conclude that these 5 residues define a high-affinity binding site in FGF-2 for fibrinogen.

Original languageEnglish (US)
Pages (from-to)2114-2120
Number of pages7
JournalBlood
Volume103
Issue number6
DOIs
StatePublished - Mar 15 2004
Externally publishedYes

Fingerprint

Fibroblast Growth Factor 2
Fibrinogen
Binding Sites
Fibroblast Growth Factor 1
Mutagenesis
Fibrin
Endothelial cells
Interchanges
Site-Directed Mutagenesis
Cell Communication
Adhesives
Endothelial Cells
Degradation
Growth

ASJC Scopus subject areas

  • Hematology

Cite this

Peng, H., Sahni, A., Fay, P., Bellum, S., Prudovsky, I., Maciag, T., & Francis, C. W. (2004). Identification of a binding site on human FGF-2 for fibrinogen. Blood, 103(6), 2114-2120. https://doi.org/10.1182/blood-2003-08-2638

Identification of a binding site on human FGF-2 for fibrinogen. / Peng, Hu; Sahni, Abha; Fay, Philip; Bellum, Stephen; Prudovsky, Igor; Maciag, Thomas; Francis, Charles W.

In: Blood, Vol. 103, No. 6, 15.03.2004, p. 2114-2120.

Research output: Contribution to journalArticle

Peng, H, Sahni, A, Fay, P, Bellum, S, Prudovsky, I, Maciag, T & Francis, CW 2004, 'Identification of a binding site on human FGF-2 for fibrinogen', Blood, vol. 103, no. 6, pp. 2114-2120. https://doi.org/10.1182/blood-2003-08-2638
Peng H, Sahni A, Fay P, Bellum S, Prudovsky I, Maciag T et al. Identification of a binding site on human FGF-2 for fibrinogen. Blood. 2004 Mar 15;103(6):2114-2120. https://doi.org/10.1182/blood-2003-08-2638
Peng, Hu ; Sahni, Abha ; Fay, Philip ; Bellum, Stephen ; Prudovsky, Igor ; Maciag, Thomas ; Francis, Charles W. / Identification of a binding site on human FGF-2 for fibrinogen. In: Blood. 2004 ; Vol. 103, No. 6. pp. 2114-2120.
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