Glycosaminoglycan affinity of the complete fibroblast growth factor family

Glycosaminoglycan affinity of the complete fibroblast growth factor family
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DOI:
10.1016/j.bbagen.2008.09.001
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发表时间:
2009-01-01
影响因子:
3
通讯作者:
Imamura, Toru
Imamura, Toru
中科院分区:
生物学3区
文献类型:
--
作者:
Asada, Masahiro;Shinomiya, Michiyo;Imamura, Toru

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背景:许多成纤维细胞生长因子家族蛋白(FGFS)与硫酸乙酰肝素/肝素(HP)亚型结合的硫酸糖糖胺聚糖(GAG)(GAGS),最近也报道了一些与软糖素硫酸盐(CS)相互作用.Methods:为了获得对这种相互作用的更多见解,我们准备了当前已知的FGF(即FGF1-FGF23),并评估了它们对HP,CS-B,CS-D和CS-E的亲和力。此外,研究了中心,肝细胞生长因子和多叶酸蛋白作为其他已知的HP结合蛋白。回报:我们发现FGF19亚家族的成员(即FGF15,19、21和23)几乎没有或没有HP的亲和力;所测试的所有其他可分泌的生长因子对HP具有很强的亲和力,这表明,它们从HP-塞磷脂柱中洗脱的情况表明,需要1.0-1.5 m NaCl。我们还发现,FGF3、6、8和22对CS-E具有很强的亲和力,而FGF5对CS-D具有中等亲和力。因此,FGF和插科打s之间的相互作用似乎比以前所理解的要多样化。一般的意义:这是值得注意的。由于这些生长因子与堵嘴的差异相互作用可能是其特定生物活性的关键决定因素。 (c)2008 Elsevier B.V.保留所有权利。
Background: Many fibroblast growth factor family proteins (FGFs) bind to the heparan sulfate/heparin (HP) subtypes of sulfated glycosaminoglycans (GAGs), and a few have recently been reported to also interact with chondroitin sulfate (CS), another sulfated GAG subtype.Methods: To gain additional insight into this interaction, we prepared all currently known FGFs (i.e., FGF1-FGF23) and assessed their affinity for HP, CS-B, CS-D and CS-E. In addition, midkine, hepatocyte growth factor and pleiotrophin were studied as other known HP-binding proteins.Results: We found that members of the FGF19 subfamily (i.e., FGF15,19, 21 and 23) had little or no affinity for HP; all of the other secretable growth factors tested had strong affinities for HP, as was indicated by the finding that their elution from HP-Sepharose columns required 1.0-1.5 M NaCl. We also found that FGF3, 6, 8 and 22 had strong affinities for CS-E, while FGF5 had a moderate affinity for CS-D. The interactions between FGFs and GAGs thus appear to be more diverse than previously understood.General significance: This is noteworthy. as the differential interactions of these growth factors with GAGs may be key determinants of their specific biological activities. (C) 2008 Elsevier B.V. All rights reserved.