The Proteinase PAPP-A has Deep Evolutionary Roots Outside of the IGF System.

ABSTRACT: The animal pappalysin metalloproteinases, PAPP-A and PAPP-A2, are highly specific regulatory enzymes of the insulin-like growth factor (IGF) system. Cleavage of their only known substrates, a subset of IGF binding proteins (IGFBPs), releases bioactive IGFI and IGFII, thus promoting IGF signaling. Stanniocalcin-1 and -2 (STC1 and STC2) are potent pappalysin inhibitors, completing the STC-PAPP-A-IGFBP-IGF axis. Utilizing homology searches and phylogenetic analyses, we examined the occurrence of pappalysins in the animal kingdom and their functional conservation. This revealed the extensive presence of pappalysins across metazoans, as well as the presence of 3 pappalysins: PAPP-A, PAPP-A2, and a third group of invertebrate pappalysins, which we name invertebrate PAPP-A (invPAPP-A). We show th

SUBMITTER: Kjeldsen CMN 

PROVIDER: S-EPMC11925022 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature