Various expression patterns of pregnancy-associated plasma protein-A

Abstract

The zinc metalloproteinase, PAPP-A was firstly identified as one of the four placental antigens of unknown function found in high concentrations in the plasma of pregnant women (Gall and Halbert, 1972), hence the name 'pregnancy-associated plasma protein-A' (Lin et al., 1974). Subsequent studies found PAPP-A mRNA to be expressed in a variety of cell types and tissues unrelated to pregnancy (Overgaard et al., 1999).Along with PAPP-A, three other (non-proteolytic) pregnancy-associated proteins were described and were named PAPP-B, -C, and -D based on positions of precipitate lines in immunodiffusion experiments. PAPP-A was shown to enhance insulin-like growth factor (IGF) action through specific cleavage of inhibitory IGF binding protein (IGFBP), primarily IGFBP-4 (Lawrence et al., 1999). Cleavage of IGFBP-4 results in loss of binding affinity for IGF, causing increased IGF bioavailability for IGF-IRmediated proliferation, survival and migration (Conover and Oxvig, 2018).