Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action
Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action
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DOI：
10.1073/pnas.94.13.6770
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发表时间：
1997-06-24
影响因子：
11.1
通讯作者：
Rubin, JS
中科院分区：
文献类型：
--
作者：
Finch, PW;He, X;Rubin, JS
卷曲多肽是一种完整的膜蛋白，最近被证明是Wnt信号分子的受体，我报告了一种新的分泌36 kDa的蛋白，该蛋白含有一个与Frizzleds的Wnt结合结构域同源的区域。该蛋白称为FrizzledRelated，Protein(FRP)，首次被鉴定为一种肝素结合多肽，可与人胚胎肺成纤维细胞条件培养液中的肝细胞生长因子/分散因子结合。这些基因编码一个313个氨基酸的多肽，含有一个约110个残基的半胱氨酸富集区，与Frizzled蛋白质的配体结合区有30-40%的同源性，FRP基因的4.4kb转录本存在于许多器官中，无论是在成体还是在胚胎发生过程中，该基因的同源基因在几种脊椎动物的DNA中都可以检测到。在生物合成研究中，FRP是分泌的，但像Wnts一样，倾向于与细胞保持联系，当在非洲爪哇早期胚胎中与几个Wnt家族成员共表达时，Frp拮抗了依赖Wnt的胚胎背部ASIS的复制。这些结果表明，FRP可能在发育过程中和成人中起到抑制Wnt作用的作用。
Frizzled polypeptides are integral membrane proteins that recently were shown to function as receptors for Wnt signaling molecules, Were, me report the identification of a novel, secreted 36-kDa protein that contains a region homologous to a putative Wnt-binding domain of Frizzleds. This protein, called Frizzled-related, protein (FRP), was first identified as a heparin-binding polypeptide that copurified with hepatocyte growth factor/scatter factor in conditioned medium from a human embryonic lung fibroblast line, Degenerate oligonucleotides, based on the NH2-terminal sequence of the purified protein, were used to isolate corresponding cDNA clones. These encoded a 313-amino acid polypeptide, containing a cysteine-rich domain of approximate to 110 residues that was 30-40% identical to the putative ligand-binding domain of Frizzled proteins, A 4.4-kb transcript of the FRP gene is present in many organs, both in the adult and during embryogenesis, and homologs of the gene are detectable in DNA from several vertebrate species, In biosynthetic studies, FRP was secreted but, like Wnts, tended to remain associated with cells, When coexpressed with several Wnt family members in early Xenopus embryos, FRP antagonized Wnt-dependent duplication of the embryonic dorsal asis. These results indicate that FRP may function as an inhibitor of Wnt action during development and in the adult.