Pregnancy-associated plasma protein-A (PAPP-A): a local regulator of IGF bioavailability through cleavage of IGFBPs.
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.
Boldt
Henning B
HB
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.
Conover
Cheryl A
CA
D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011266:Pregnancy-Associated Plasma Protein-A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013002:Somatomedins / Q000378:metabolism*; D014018:Tissue Distribution
D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D011266:Pregnancy-Associated Plasma Protein-A