Not all perlecans are created equal - Interactions with fibroblast growth factor (FGF) 2 and FGF receptors
Not all perlecans are created equal - Interactions with fibroblast growth factor (FGF) 2 and FGF receptors
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DOI：
10.1074/jbc.m111826200
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发表时间：
2002-04-26
影响因子：
4.8
通讯作者：
Whitelock, J
中科院分区：
文献类型：
--
作者：
Knox, S;Merry, C;Whitelock, J
人基底膜硫酸乙酰肝素蛋白聚糖（HSPG）串珠素通过其硫酸乙酰肝素（HS）链结合并激活成纤维细胞生长因子（FGF）-2。在这里，我们表明，从三个细胞来源免疫纯化的串珠具有不同的HS结构，随后不同的FGF-2的结合和激活能力。从人脐动脉内皮细胞（HUAEC）和连续内皮细胞系（C11 STH）中分离的串珠素单独或与FGFR α 1-IIIc或FGFR 3 α-IIIc复合结合相似量的FGF-2。两种串珠素均刺激表达FGFR 1b/c的BaF 3细胞系的生长;然而，仅HUAEC串珠素刺激表达FGFR 3c的那些细胞，表明串珠素的来源赋予FGF和FGFR结合特异性。尽管FGF-2活化存在这些差异，但两种串珠素的2-O-和6-O-硫酸化水平相似。有趣的是，从结肠癌细胞系中分离的能够结合FGF-2的串珠素不能激活任何BaF 3细胞系，除非从蛋白质核心中除去HS。HS链在用肝素酶III消化后也表现出更大的生物活性。总的来说，这些数据清楚地表明，HS修饰单个PG的生物活性取决于其细胞来源，并且结构的细微变化（包括次级相互作用）对生物活性具有深远的影响。
Human basement membrane heparan sulfate proteoglycan (HSPG) perlecan binds and activates fibroblast growth factor (FGF)-2 through its heparan sulfate (HS) chains. Here we show that perlecans immunopurified from three cellular sources possess different HS structures and subsequently different FGF-2 binding and activating capabilities. Perlecan isolated from human umbilical arterial endothelial cells (HUAEC) and a continuous endothelial cell line (C11 STH) bound similar amounts of FGF-2 either alone or complexed with FGFRalpha1-IIIc or FGFR3alpha-IIIc. Both perlecans stimulated the growth of BaF3 cell lines expressing FGFR1b/c; however, only HUAEC perlecan stimulated those cells expressing FGFR3c, suggesting that the source of perlecan confers FGF and FGFR binding specificity. Despite these differences in FGF-2 activation, the level of 2-O- and 6-O-sulfation was similar for both perlecans. Interestingly, perlecan isolated from a colon carcinoma cell line that was capable of binding FGF-2 was incapable of activating any BaF3 cell line unless the HS was removed from the protein core. The HS chains also exhibited greater bioactivity after digestion with heparinase III. Collectively, these data clearly demonstrate that the bioactivity of HS decorating a single PG is dependent on its cell source and that subtle changes in structure including secondary interactions have a profound effect on biological activity.