Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein
Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein
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DOI：
10.1074/jbc.m209256200
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发表时间：
2003-01-24
影响因子：
4.8
通讯作者：
Sakai, LY
中科院分区：
文献类型：
--
作者：
Isogai, Z;Ono, RN;Sakai, LY
潜伏性转化生长因子6结合蛋白1（LTBP-1）将转化生长因子β的潜在复合物靶向细胞外基质，其中潜伏性细胞因子随后通过几种不同的机制激活。原纤蛋白是细胞外基质大分子，其主要功能是结构：原纤蛋白组装成在结缔组织间隙中普遍存在的超微结构上不同的微纤维。LTBP和原纤维蛋白是高度同源的分子，并且已经报道了在培养细胞的基质中的共定位。为了解决LTBP-1是否在结构上像原纤维蛋白一样起作用，从组织中提取微纤维并进行免疫化学分析。此外，进行结合研究以确定LTBP-1是否与原纤维蛋白相互作用。LTBP-1没有检测到提取珠串微纤维，表明LTBP-I是不是一个完整的结构组成部分的微纤维。然而，结合研究表明LTBP-1和原纤维蛋白之间的相互作用。结合位点在LTBP-1C端的三个结构域内，并且在LBP-1中，该位点被限定在靠近N端的四个结构域内。免疫定位数据与LTBP-1是存在于某些组织中但不存在于其他组织中的原纤维蛋白相关蛋白的假设一致。在不表达LTBP-1的组织中，LTBP-4可以取代LTBP-1，因为LTBP-4的C-末端同样很好地结合到白蛋白。提出了一个描述LTBP-1和微纤维中的LTBP-1之间关系的模型。
Latent transforming growth factor 6-binding protein 1 (LTBP-1) targets latent complexes of transforming growth factor beta to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. Fibrillins are extracellular matrix macromolecules whose primary function is architectural: fibrillins assemble into ultrastructurally distinct microfibrils that are ubiquitous in the connective tissue space. LTBPs and fibrillins are highly homologous molecules, and colocalization in the matrix of cultured cells has been reported. To address whether LTBP-1 functions architecturally like fibrillins, microfibrils were extracted from tissues and analyzed immunochemically. In addition, binding studies were conducted to determine whether LTBP-1 interacts with fibrillins. LTBP-1 was not detected in extracted beaded-string microfibrils, suggesting that LTBP-I is not an integral structural component of microfibrils. However, binding studies demonstrated interactions between LTBP-1 and fibrillins. The binding site was within three domains of the LTBP-1 C terminus, and in fibrillin-1 the site was defined within four domains near the N terminus. Immunolocalization data were consistent with the hypothesis that LTBP-1 is a fibrillin-associated protein present in certain tissues but not in others. In tissues where LTBP-1 is not expressed, LTBP-4 may substitute for LTBP-1, because the C-terminal end of LTBP-4 binds equally well to fibrillin. A model depicting the relationship between LTBP-1 and fibrillin microfibrils is proposed.