Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells
Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells
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DOI：
10.1128/mcb.12.1.240-247.1992
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发表时间：
1992-01
影响因子：
5.3
通讯作者：
D. Ornitz;A. Yayon;J. Flanagan;C. Svahn;E. Levi;P. Leder
中科院分区：
文献类型：
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作者：
D. Ornitz;A. Yayon;J. Flanagan;C. Svahn;E. Levi;P. Leder
肝素是碱性成纤维细胞生长因子（bFGF）与缺乏细胞表面硫酸乙酰肝素蛋白聚糖的细胞上的高亲和力受体结合所必需的。因此，这种肝素的需求可以在没有其他细胞表面分子的情况下进行评估，我们设计了一个简单的分析的基础上，用胎盘碱性磷酸酶标记的基因工程可溶形式的鼠FGF受体1（mFR 1）。使用该测定，我们表明FGF-受体结合对肝素具有绝对需求。通过使用一种表达mFR 1的精氨酸依赖性淋巴样细胞系，我们还发现FGF诱导的促有丝分裂活性是肝素依赖性的。此外，我们测试了一系列确定长度的小肝素寡糖支持bFGF受体结合和生物活性的能力。我们发现，肝素寡糖与少至8个糖残基是足以支持这些活动。我们还证明了肝素促进FGF二聚化，这一特性可能对受体活化很重要。
Heparin is required for the binding of basic fibroblast growth factor (bFGF) to high-affinity receptors on cells deficient in cell surface heparan sulfate proteoglycan. So that this heparin requirement could be evaluated in the absence of other cell surface molecules, we designed a simple assay based on a genetically engineered soluble form of murine FGF receptor 1 (mFR1) tagged with placental alkaline phosphatase. Using this assay, we showed that FGF-receptor binding has an absolute requirement for heparin. By using a cytokine-dependent lymphoid cell line engineered to express mFR1, we also showed that FGF-induced mitogenic activity is heparin dependent. Furthermore, we tested a series of small heparin oligosaccharides of defined lengths for their abilities to support bFGF-receptor binding and biologic activity. We found that a heparin oligosaccharide with as few as eight sugar residues is sufficient to support these activities. We also demonstrated that heparin facilitates FGF dimerization, a property that may be important for receptor activation.