TY - JOUR
T1 - ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3.
AU - Loechel, F
AU - Fox, J W
AU - Murphy, G
AU - Albrechtsen, R
AU - Wewer, U M
N1 - Keywords: 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
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
U2 - 10.1006/bbrc.2000.3835
DO - 10.1006/bbrc.2000.3835
M3 - Journal article
C2 - 11095942
SN - 0006-291X
VL - 278
SP - 511
EP - 515
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -