妊娠相关血浆蛋白A
受体
劈理(地质)
胰岛素样生长因子结合蛋白
生物
细胞生物学
功能(生物学)
生长因子
金属蛋白酶
怀孕
内分泌学
胰岛素样生长因子
内科学
化学
基质金属蛋白酶
生物化学
遗传学
胎儿
医学
古生物学
孕早期
断裂(地质)
作者
Cheryl A. Conover,Claus Oxvig
出处
期刊:Endocrine Reviews
[The Endocrine Society]
日期:2023-06-02
卷期号:44 (6): 1012-1028
被引量:7
标识
DOI:10.1210/endrev/bnad017
摘要
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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