Bashir M M, Han M D, Abrams W R, Tucker T, Ma R I, Gibson M, Ritty T, Mecham R, Rosenbloom J
Department of Anatomy and Histology, School of Dental Medicine, University of Philadelphia, PA 19104, USA.
Int J Biochem Cell Biol. 1996 May;28(5):531-42. doi: 10.1016/1357-2725(95)00167-0.
Transforming growth factor (TGF)-beta is secreted as an inactive complex, which frequently contains a large molecular weight binding protein designated latent TGF-beta-binding protein (LTBP). Recently, the LTBPs have been shown to be a gene family that contains three known members and exhibits a multidomain structure containing cysteine-rich motifs that are also found in the fibrillin gene family. The present work seeks to characterize the gene encoding LTBP-2 and to compare its features to that of the other LTBPs and to the fibrillins. Human fibroblast libraries were used to isolate cDNA encoding LTBP-2 which was then used to identify LTBP-2 transcripts and to isolate the corresponding LTBP-2 gene. The cloned cDNA encodes a 195 kDa protein containing 20 epidermal growth factor (EGF)-like repeats, three repeats containing eight cysteines, and one segment that appears to be a hybrid of the two. Single exons encode EGF repeats while the eight-cysteine repeats are encoded in two exons. Northern analysis identified two transcripts of 7.5 and 9.0 kb, with the presently analyzed cDNA probably corresponding to the 7.5 transcript. Phylogenetic sequence comparisons demonstrated that LTBP-3 is more similar to LTBP-1 than LTBP-2, while LTBP-2 shows the most similarity to the fibrillins. These analyses suggest that LTBP-1 diverged from LTBP-3, and that LTBP-2 diverged from LTBP-1. Within the fibrillin family, fibrillin-1 is nearest to the LTBPs. While the domain structure of LTBP-2 is similar to that of the other LTBPs, LTBP-2 possesses unique regions that make it the largest member of the LTBP family. LTBP-2 may have dual functions as a member of the TGF-beta latent complex and as a structural component of microfibrils.
转化生长因子（TGF）-β以无活性复合物的形式分泌，该复合物通常包含一种称为潜伏TGF-β结合蛋白（LTBP）的大分子结合蛋白。最近，LTBP已被证明是一个基因家族，包含三个已知成员，并呈现出多结构域结构，其中含有在原纤维蛋白基因家族中也发现的富含半胱氨酸的基序。本研究旨在鉴定编码LTBP-2的基因，并将其特征与其他LTBP以及原纤维蛋白的特征进行比较。利用人成纤维细胞文库分离编码LTBP-2的cDNA，然后用其鉴定LTBP-2转录本并分离相应的LTBP-2基因。克隆的cDNA编码一种195 kDa的蛋白质，含有20个表皮生长因子（EGF）样重复序列、三个含八个半胱氨酸的重复序列以及一个似乎是两者杂交的片段。单个外显子编码EGF重复序列，而八个半胱氨酸的重复序列由两个外显子编码。Northern分析鉴定出7.5 kb和9.0 kb的两种转录本，目前分析的cDNA可能对应于7.5 kb的转录本。系统发育序列比较表明，LTBP-3与LTBP-1比与LTBP-2更相似，而LTBP-2与原纤维蛋白的相似性最高。这些分析表明，LTBP-1与LTBP-3分化，而LTBP-2与LTBP-1分化。在原纤维蛋白家族中，原纤维蛋白-1与LTBP最接近。虽然LTBP-2的结构域结构与其他LTBP相似，但LTBP-2拥有独特区域，使其成为LTBP家族中最大的成员。LTBP-2可能具有作为TGF-β潜伏复合物成员和微原纤维结构成分的双重功能。
