IGF dependent modulation of IGF binding protein (IGFBP) proteolysis by pregnancy-associated plasma protein-A (PAPP-A): Multiple PAPP-A-IGFBP interaction sites

► Acidic residues of PAPP-A are required for substrate cleavage. ► Structural calcium ions are suggested to be implicated in interaction with IGFBPs. ► IGF-IGFBP interaction determines protease-substrate binding. ► The central and the C-terminal domains of IGFBPs mediate IGF dependent proteolysis.