ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3.
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.
Mesh Terms:
ADAM Proteins, Amino Acid Sequence, Disintegrins, Female, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Protein 5, Membrane Proteins, Metalloendopeptidases, Peptide Fragments, Pregnancy, Recombinant Proteins, Substrate Specificity, Tissue Inhibitor of Metalloproteinase-3
ADAM Proteins, Amino Acid Sequence, Disintegrins, Female, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Protein 5, Membrane Proteins, Metalloendopeptidases, Peptide Fragments, Pregnancy, Recombinant Proteins, Substrate Specificity, Tissue Inhibitor of Metalloproteinase-3
Biochem. Biophys. Res. Commun.
Date: Nov. 30, 2000
PubMed ID: 11095942
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