The Pregnancy-Associated Plasma Protein-A (PAPP-A) Story.

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2023-11-09 DOI:10.1210/endrev/bnad017
Cheryl A Conover, Claus Oxvig
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引用次数: 3

Abstract

Pregnancy-associated plasma protein-A (PAPP-A) was first identified in the early 1970s as a placental protein of unknown function, present at high concentrations in the circulation of pregnant women. In the mid-to-late 1990s, PAPP-A was discovered to be a metzincin metalloproteinase, expressed by many nonplacental cells, that regulates local insulin-like growth factor (IGF) activity through cleavage of high-affinity IGF binding proteins (IGFBPs), in particular IGFBP-4. With PAPP-A as a cell surface-associated enzyme, the reduced affinity of the cleavage fragments results in increased IGF available to bind and activate IGF receptors in the pericellular environment. This proteolytic regulation of IGF activity is important, since the IGFs promote proliferation, differentiation, migration, and survival in various normal and cancer cells. Thus, there has been a steady growth in investigation of PAPP-A structure and function outside of pregnancy. This review provides historical perspective on the discovery of PAPP-A and its structure and cellular function, highlights key studies of the first 50 years in PAPP-A research, and introduces new findings from recent years.

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妊娠相关血浆蛋白a (pap - a)的故事。
妊娠相关血浆蛋白-a (PAPP-A)在20世纪70年代初首次被发现是一种功能未知的胎盘蛋白,高浓度存在于孕妇的血液循环中。在20世纪90年代中后期,PAPP-A被发现是一种由许多非胎盘细胞表达的metzincin金属蛋白酶,通过切割高亲和力的IGF结合蛋白(igfbp),特别是IGFBP-4,来调节局部胰岛素样生长因子(IGF)的活性。由于PAPP-A是一种细胞表面相关酶,切割片段的亲和力降低导致可结合并激活细胞周围环境中IGF受体的IGF增加。IGF活性的蛋白水解调节是重要的,因为IGF促进各种正常细胞和癌细胞的增殖、分化、迁移和存活。因此,对妊娠期外ppap - a结构和功能的研究稳步增长。本文综述了PAPP-A的发现历史及其结构和细胞功能,重点介绍了前50年PAPP-A研究的重点研究,并介绍了近年来的新发现。
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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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