ACIDIC AND BASIC FIBROBLAST GROWTH-FACTOR BIND WITH DIFFERING AFFINITY TO THE SAME HEPARAN-SULFATE PROTEOGLYCAN ON BALB/C 3T3 CELLS - IMPLICATIONS FOR POTENTIATION OF GROWTH-FACTOR ACTION BY HEPARIN
ACIDIC AND BASIC FIBROBLAST GROWTH-FACTOR BIND WITH DIFFERING AFFINITY TO THE SAME HEPARAN-SULFATE PROTEOGLYCAN ON BALB/C 3T3 CELLS - IMPLICATIONS FOR POTENTIATION OF GROWTH-FACTOR ACTION BY HEPARIN
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DOI：
10.1002/jcb.240580103
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发表时间：
1995-05-01
影响因子：
4
通讯作者：
PARISH, CR
中科院分区：
文献类型：
--
作者：
BROWN, KJ;HENDRY, IA;PARISH, CR
细胞表面上的硫酸乙酰肝素蛋白聚糖充当酸性和碱性成纤维细胞生长因子（FGF）的低亲和力结合位点[Moscatelli（1987）：J Cell Physiol 131：123-130]，并且在FGF与FGF受体（FGFR）的相互作用中起重要作用。在这项研究中，FGF与细胞表面硫酸乙酰肝素蛋白聚糖的相互作用的几个方面进行了检查。相互交叉阻断研究表明，酸性成纤维细胞生长因子（aFGF）和碱性成纤维细胞生长因子（bFGF）结合相同或密切相关的硫酸乙酰肝素基序的BALB/c 3 T3细胞表面硫酸乙酰肝素蛋白多糖。然而，这两种生长因子对这些硫酸乙酰肝素蛋白聚糖的结合亲和力差异很大，竞争结合数据表明aFGF对3 T3硫酸乙酰肝素蛋白聚糖的亲和力比bFGF低4.7倍。随后的解离动力学研究表明，bFGF从FGFR解离至少比aFGF慢10倍，而在通过肝素酶处理去除细胞表面硫酸乙酰肝素蛋白聚糖后，两种FGF的解离速率相似且快速。这些结果支持细胞表面硫酸乙酰肝素蛋白聚糖稳定FGF与FGFR的相互作用的概念，可能是通过形成三元复合物。(C)1995 Wiley-Liss，Inc.
Heparan sulfate proteoglycans on the cell surface act as low affinity binding sites for acidic and basic fibroblast growth factor (FGF) [Moscatelli (1987): J Cell Physiol 131:123-130] and play an important role in the interaction of FGF with the FGF receptor (FGFR). In this study, several aspects of the interaction of FGFs with cell surface heparan sulfate proteoglycans were examined. Reciprocal cross blocking studies demonstrated that acidic FGF (aFGF) and basic FGF (bFGF) bind to identical or closely associated heparan sulfate motifs on BALB/c 3T3 cell surface heparan sulfate proteoglycans. However, the binding affinity of the two growth factors for these heparan sulfate proteoglycans differs considerably, competition binding data indicating that aFGF has a 4.7-fold lower affinity than bFGF for 3T3 heparan sulfate proteoglycan. Subsequent studies of dissociation kinetics demonstrated that bFGF dissociates from the FGFR at least 10-fold slower than aFGF, whereas, following removal of cell surface heparan sulfate proteoglycans by heparinase treatment, the dissociation rate of both FGFs is similar and rapid. These results support the concept that cell surface heparan sulfate proteoglycans stabilize the interaction of FGF with FGFR, possibly by the formation of a ternary complex. (C) 1995 Wiley-Liss, Inc.