TY - JOUR
T1 - Pregnancy-associated plasma protein-A (PAPP-A)
T2 - A local regulator of IGF bioavailability through cleavage of IGFBPs
AU - Boldt, Henning B.
AU - Conover, Cheryl A.
N1 - Funding Information:
This work was supported, in part, by the Danish Research Council of Health and Disease (to HBB) and by National Institutes of Health Grant HL74871 (to CAC).
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
KW - IGF binding protein
KW - Insulin-like growth factor
KW - Pappalysin
KW - Pregnancy associated plasma protein-A
KW - Protease
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U2 - 10.1016/j.ghir.2006.11.003
DO - 10.1016/j.ghir.2006.11.003
M3 - Review article
C2 - 17218136
AN - SCOPUS:33847233874
SN - 1096-6374
VL - 17
SP - 10
EP - 18
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
IS - 1
ER -