Boldt Henning B, Conover Cheryl A
Division of Endocrinology, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, 5-194 Joseph, Rochester, MN 55905, USA.
Growth Horm IGF Res. 2007 Feb;17(1):10-8. doi: 10.1016/j.ghir.2006.11.003. Epub 2007 Jan 10.
Pregnancy-associated plasma protein-A (PAPP-A) was originally isolated in 1974, as one of four proteins of placental origin found in high concentrations in the blood of pregnant women. In the early 1990s several laboratories reported novel protease activity against insulin-like growth factor binding protein-4 (IGFBP-4) in media conditioned by several cell types. This activity was unique, as it appeared to require the presence of IGF to cleave IGFBP-4. In 1999, this IGF-dependent IGFBP-4 protease activity was isolated from human fibroblast conditioned media and identified as PAPP-A. Subsequently, PAPP-A was shown to be expressed by a variety of cell types, and thus no longer could be considered to be just "pregnancy-associated". This review will describe what is currently known about the structure of PAPP-A and about its function as an IGFBP protease, with a focus on new insights obtained through study of a PAPP-A knock-out mouse model and on potential clinical applications.
妊娠相关血浆蛋白A（PAPP-A）最初于1974年被分离出来，是在孕妇血液中发现的四种胎盘来源蛋白之一。20世纪90年代初，几个实验室报告称，几种细胞类型条件培养基中存在针对胰岛素样生长因子结合蛋白-4（IGFBP-4）的新型蛋白酶活性。这种活性很独特，因为它似乎需要IGF的存在才能切割IGFBP-4。1999年，这种IGF依赖性IGFBP-4蛋白酶活性从人成纤维细胞条件培养基中分离出来，并被鉴定为PAPP-A。随后，研究表明PAPP-A可由多种细胞类型表达，因此不能再被认为仅仅是“妊娠相关的”。本综述将描述目前已知的PAPP-A结构及其作为IGFBP蛋白酶的功能，重点关注通过研究PAPP-A基因敲除小鼠模型获得的新见解以及潜在的临床应用。
