Binding of insulin-like growth factor (IGF) I or II to IGF-binding protein-2 enables it to bind to heparin and extracellular matrix.
Binding of insulin-like growth factor (IGF) I or II to IGF-binding protein-2 enables it to bind to heparin and extracellular matrix.
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DOI：
10.1210/endo.137.11.8895319
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发表时间：
1996-11
期刊：
影响因子：
4.8
通讯作者：
Takami Arai;W. Busby;D. Clemmons
中科院分区：
文献类型：
--
作者：
Takami Arai;W. Busby;D. Clemmons
胰岛素样生长因子（IGF）结合蛋白-2 （IGFBP-2）由几种也分泌IGF- i或IGF- ii的细胞分泌。IGF-I或IGF-II与IGFBP-2的结合已被证明可以改变它们的作用。虽然IGFBP-2不是细胞外基质（ECM）的丰富成分，但它很容易通过免疫组织化学染色在几种上皮细胞类型的基底膜中定位。我们之前已经证明IGFBP-5与糖胺聚糖结合，并与ECM和基底膜中含有的蛋白聚糖结合。在这些研究中，我们无法证明IGFBP-2与糖胺聚糖的关联。在这项研究中，我们报道了如果IGF-I或IGF-II也包含在孵育缓冲液中，IGFBP-2与肝素结合。IGFBP-1、-3、-4或-5在IGF-I或IGF-II存在时没有增加肝素结合。igf - 1与IGFBP-2的摩尔比为2:1，可检测IGFBP-2与肝素的结合。可溶性肝素或硫酸肝素可抑制肝素- sepharose与肝素- sepharose的结合，但在伊杜醛酸环的2或3位不含o -连接硫酸基团的糖胺聚糖则不能。合成的含有肝素结合结构域的IGFBP-5肽也能抑制与肝素的结合，但不受不与肝素结合的电荷质量比相同的肽的抑制。如果添加IGF-I或IGF-II， IGFBP-2与人成纤维细胞ECM的结合似乎具有显著的生理意义。IGF- ii在促进结合相互作用方面比IGF- i更有效，而des(1-3)-IGF-I或胰岛素没有作用，这表明IGF与IGFBP-2结合才能检测到这种作用。总之，IGFBP-2与糖胺聚糖的结合依赖于IGF-I和IGF-II与IGFBP-2的结合。这表明IGFBP-2经历了一个暴露糖胺聚糖结合结构域的构象变化。这可能提供了IGFBP-2在细胞周围环境中局部富集的机制。
Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) is secreted by several cell types that also secrete IGF-I or IGF-II. The binding of IGF-I or IGF-II to IGFBP-2 has been shown to alter their actions. Although IGFBP-2 is not an abundant component of the extracellular matrix (ECM), it is easily localized by immunohistochemical staining in basement membranes of several epithelial cell types. We have previously shown that IGFBP-5 associates with glycosaminoglycans and binds to proteoglycans that are contained in ECM and basement membranes. In those studies we were unable to demonstrate an association of IGFBP-2 with glycosaminoglycans. In this study we report that IGFBP-2 binds to heparin if IGF-I or IGF-II is also included in the incubation buffer. IGFBP-1, -3, -4, or -5 did not have increased heparin binding in the presence of IGF-I or IGF-II. The binding of IGFBP-2 to heparin was detectable using an IGF-I to IGFBP-2 molar ratio of 2:1. Binding to heparin-Sepharose could be inhibited by soluble heparin or heparan sulfate, but not by glycosaminoglycans that do not contain O-linked sulfate groups in the 2 or 3 position of the iduronic acid ring. Binding was also inhibited by a synthetic IGFBP-5 peptide that contained a heparin-binding domain, but not by a peptide with an identical charge to mass ratio that does not bind to heparin. Binding appeared to be physiologically significant, as IGFBP-2 bound to human fibroblast ECM if IGF-I or IGF-II was added. IGF-II was more potent than IGF-I in facilitating the binding interaction, and des(1-3)-IGF-I or insulin had no effect, suggesting that IGF binding to IGFBP-2 is required for this effect to be detected. In summary, IGFBP-2 binding to glycosaminoglycans is dependent upon binding of IGF-I and IGF-II to IGFBP-2. This suggests that IGFBP-2 undergoes a conformational change that exposes a glycosaminoglycan-binding domain. This could provide a mechanism for focally concentrating IGFBP-2 in the pericellular environment.