STRUCTURE-FUNCTION RELATIONSHIP OF BASIC FIBROBLAST GROWTH-FACTOR - SITE-DIRECTED MUTAGENESIS OF A PUTATIVE HEPARIN-BINDING AND RECEPTOR-BINDING REGION

被引：30

作者：

PRESTA, M ^{[1
]}

STATUTO, M ^{[1
]}

ISACCHI, A ^{[1
]}

CACCIA, P ^{[1
]}

POZZI, A ^{[1
]}

GUALANDRIS, A ^{[1
]}

RUSNATI, M ^{[1
]}

BERGONZONI, L ^{[1
]}

SARMIENTOS, P ^{[1
]}

机构：

[1] FARMITALIA CARLO ERBA SPA,DEPT BIOTECHNOL,MILAN,ITALY

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1992年 / 185卷 / 03期

关键词：

D O I：

10.1016/0006-291X(92)91739-D

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Basic residues Arg-118, Lys-119, Lys-128, and Arg-129 within a putative heparin-binding and receptor-binding region of the 155-amino acid form of basic fibroblast growth factor (bFGF) have been changed to neutral glutamine residues by site-directed mutagenesis of the human bFGF cDNA. The bFGF mutant (M6B-bFGF) was expressed in E. coli and purified to homogeneity. When compared to wild type bFGF, M6B-bFGF showed in cultured endothelial cells a similar receptor-binding capacity and mitogenic activity, but a reduced affinity for heparin-like low affinity binding sites, a reduced chemotactic activity, and a reduced capacity to induce the production of urokinase-type plasminogen activator. In vivo, M6B-bFGF lacked a significant angiogenic activity. Modifications of both the primary and the tertiary structure of bFGF appear to be responsible for the modified biological properties of M6B-bFGF, thus confirming the possibility to dissociate at the structural level some of the biological activities exerted by bFGF on endothelial cells. © 1992.

引用

页码：1098 / 1107

页数：10

共 27 条

[1] RECEPTOR-BINDING AND HEPARIN-BINDING DOMAINS OF BASIC FIBROBLAST GROWTH-FACTOR [J].