ADAM 12-S Cleaves IGFBP-3 and IGFBP-5 and Is Inhibited by TIMP-3

• DOI: 10.1006/bbrc.2000.3835
• Publication Date: 2002-09-16T14:49:19Z
• Authors: Frosty Loechel; Jay W. Fox; Gillian Murphy; Reidar Albrechtsen; Ulla M. Wewer
• Keywords: Proteolysis; Cleavage (geology); Cleave

ADAMs are a family of multidomain proteins having proteolytic and cell adhesion activities. We have previously shown that ADAM 12-S, the secreted soluble form of human ADAM 12, is a catalytically active protease. We now describe the purification of full-length recombinant ADAM 12-S and demonstrate that it cleaves insulin-like growth factor binding protein-3 (IGFBP-3). This result supports a role for ADAM 12-S in the degradation of IGFBP-3 in the blood of pregnant women. Furthermore, we tested for proteolysis of other members of the IGF binding protein family and found that ADAM 12-S cleaves IGFBP-5 in addition to IGFBP-3, but does not cleave IGFBP-1, -2, -4, or -6. ADAM 12-S may therefore be the IGFBP-5 protease that is secreted by osteoblasts and other cells. Cleavage of both IGFBP-3 and -5 by ADAM 12-S was inhibited by TIMP-3, raising the possibility that TIMP-3 is a physiological inhibitor of ADAM 12-S.