Zhou R, Diehl D, Hoeflich A, Lahm H, Wolf E
Institute of Molecular Animal Breeding and Biotechnology, Gene Center of the University of Munich, 81377 Munich, Germany.
J Endocrinol. 2003 Aug;178(2):177-93. doi: 10.1677/joe.0.1780177.
IGFs have multiple functions regarding cellular growth, survival and differentiation under different physiological and pathological conditions. IGF effects are modulated systemically and locally by six high-affinity IGF-binding proteins (IGFBP-1 to -6). Despite their structural similarity, each IGFBP has unique properties and exhibits specific functions. IGFBP-4, the smallest IGFBP, exists in both non-glycosylated and N-glycosylated forms in all biological fluids. It is expressed by a wide range of cell types and tIssues, and its expression is regulated by different mechanisms in a cell type-specific manner. IGFBP-4 binds IGF-I and IGF-II with similar affinities and inhibits their actions under almost all in vitro and in vivo conditions. In this review, we summarize the available data regarding the following aspects of IGFBP-4: genomic organization, protein structure-function relationship, expression and its regulation, as well as IGF-dependent and -independent actions. The biological significance of IGFBP-4 for reproductive physiology, bone formation, renal pathophysiology and cancer is discussed.
在不同的生理和病理条件下，胰岛素样生长因子（IGFs）在细胞生长、存活和分化方面具有多种功能。IGF的作用受到六种高亲和力IGF结合蛋白（IGFBP - 1至 - 6）的全身和局部调节。尽管它们结构相似，但每种IGFBP都具有独特的特性并表现出特定的功能。IGFBP - 4是最小的IGFBP，在所有生物体液中均以非糖基化和N - 糖基化形式存在。它由多种细胞类型和组织表达，其表达在细胞类型特异性的方式下受到不同机制的调节。IGFBP - 4以相似的亲和力结合IGF - I和IGF - II，并在几乎所有体外和体内条件下抑制它们的作用。在这篇综述中，我们总结了关于IGFBP - 4以下方面的现有数据：基因组组织、蛋白质结构 - 功能关系、表达及其调节，以及IGF依赖性和非依赖性作用。讨论了IGFBP - 4对生殖生理学、骨形成、肾脏病理生理学和癌症的生物学意义。
