Cloning and characterization of Xenopus laevis proprotein convertases and identification of endogenous convertases of bone morphogenetic protein 4

BMP4, a highly conserved TGFβ family ligand, requires proteolytic cleavage by proprotein convertases (PCs) for activation. ProBMP4 is processed first at the S1 site and then at the upstream S2 site, which regulates BMP4 activity in a tissue‑specific manner. Using Xenopus, we identified the PCs responsible for these cleavages: furin and PC6 cleave both S1 and S2, while a third enzyme, likely PC7, selectively cleaves S1 in embryos. These findings suggest that constitutive S1 cleavage by broadly expressed PC7, combined with S1+S2 cleavage by tissue‑restricted furin or PC6, enables tissue‑specific regulation of BMP4 signaling.