Morén A, Olofsson A, Stenman G, Sahlin P, Kanzaki T, Claesson-Welsh L, ten Dijke P, Miyazono K, Heldin C H
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
J Biol Chem. 1994 Dec 23;269(51):32469-78.
Latent transforming growth factor-beta (TGF-beta)-binding protein (LTBP) is a component of the latent TGF-beta complex in human platelets. LTBP is composed of two different cysteine-rich repeat sequences, i.e. epidermal growth factor (EGF)-like repeats and a repeat containing 8 cysteine residues. The overall structure of LTBP is similar to those of the microfibrillar proteins fibrillin-1 and fibrillin-2. Here we report the identification of a novel protein termed LTBP-2, which is structurally related to LTBP. cDNA for LTBP-2 was obtained from human foreskin fibroblast cDNA libraries using a fragment of the LTBP cDNA as a probe. LTBP-2 is composed of 20 EGF-like repeats and four copies of the 8-cysteine repeat. The amino acid sequence of LTBP-2 is 41% identical to that of LTBP and 25% identical to that of fibrillin-1. LTBP-2 is synthesized as a 240-kDa protein by human foreskin fibroblasts and also by COS cells transfected with the isolated LTBP-2 cDNA. Similar to LTBP, a considerable part of LTBP-2 was found to be associated with extracellular matrix. Co-transfection of cDNAs for LTBP-2 and TGF-beta 1 revealed that LTBP-2 forms a high molecular weight complex with the TGF-beta 1 precursor. The LTBP-2 gene was assigned to chromosome 14q24. These results indicate that different forms of latent TGF-beta complexes occur and suggest that the different associated proteins may function to target the complexes to specific sites.
潜伏转化生长因子-β（TGF-β）结合蛋白（LTBP）是人类血小板中潜伏TGF-β复合物的一个组成部分。LTBP由两种不同的富含半胱氨酸的重复序列组成，即表皮生长因子（EGF）样重复序列和一个含有8个半胱氨酸残基的重复序列。LTBP的整体结构与微原纤维蛋白原纤维蛋白-1和原纤维蛋白-2的结构相似。在此我们报告了一种名为LTBP-2的新型蛋白质的鉴定，它在结构上与LTBP相关。使用LTBP cDNA片段作为探针，从人包皮成纤维细胞cDNA文库中获得了LTBP-2的cDNA。LTBP-2由20个EGF样重复序列和4个8-半胱氨酸重复序列拷贝组成。LTBP-2的氨基酸序列与LTBP的氨基酸序列有41%的同一性，与原纤维蛋白-1有25%的同一性。LTBP-2由人包皮成纤维细胞以及用分离的LTBP-2 cDNA转染的COS细胞合成为一种240 kDa的蛋白质。与LTBP相似，发现相当一部分LTBP-2与细胞外基质相关。LTBP-2和TGF-β1的cDNA共转染显示，LTBP-2与TGF-β1前体形成高分子量复合物。LTBP-2基因定位于14号染色体q24。这些结果表明存在不同形式的潜伏TGF-β复合物，并提示不同的相关蛋白可能起到将复合物靶向特定部位的作用。
