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Claus Oxvig

PAPP-A and the IGF system / La PAPP-A et le système des IGFs

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  • Philippe Monget, Institut national de la recherche agronomique, physiologie de la reproduction et des comportements, 37380 Nouzilly, France. Electronic address: pmonget@tours.inra.fr.
  • ,
  • Claus Oxvig

Firstly discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in multiple tissues. PAPP-A is a metalloproteinase that is able to specifically cleave three insulin-like growth factor binding proteins (IGFBPs): IGFBP-2, -4 and -5. PAPP-A binds tightly to glycosaminoglycans present on the surface of cells, thus functioning within tissues as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. Pro-MBP and stanniocalcin-2 (STC2) appear to be the main inhibitors of PAPP-A activity, by forming a covalent complex with the protease. According to in vivo experiments, IGFBP-4 is believed to be the main PAPP-A substrate to regulate IGF bioavailability. The regulation of PAPP-A includes transcriptional control of its gene, competing reactions with other IGFBPs potentially sequestering IGF from IGFBP-4 and hence antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP-A. Finally, PAPP-A may serve as a therapeutic target to indirectly inhibit IGF signalling in tissues where this is driven by increased PAPP-A activity. By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible.

Original languageEnglish
JournalAnnales d'Endocrinologie
Volume77
Issue2
Pages (from-to)90-96
Number of pages7
ISSN0003-4266
DOIs
Publication statusPublished - Jun 2016

    Research areas

  • Journal Article

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