THE OVINE PANCREATIC PROTEIN WHICH BINDS INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 IS PROCARBOXYPEPTIDASE-A

Insulin-like growth factor binding protein-3 (IGFBP-3) is known to mod ulate the actions of insulin-like growth factors (IGF)-I and -II at th e level of the cell. Proposed mechanisms include association of IGFBP- 3 with cell surface proteoglycan, with cell surface binding proteins, proteolysis and/or internalization of IGFBP-3. In previous studies we have characterized a protein of 40 kDa in extracts of ovine pancreas a nd muscle which binds IGFBP-3 on ligand blot analyses. This paper repo rts the identity of the pancreatic species as procarboxypeptidase A (p eptidyl-L-amino acid hydrolase, E.C. 3.4.17.1; proCPA). Identity was e stablished by amino terminal sequence analysis, binding studies with p ure bovine carboxypeptidase A (CPA) and observations that the binding activity was present in pancreatic secretions consistent with the role of proCPA as a secretory zymogen. The binding activity was inhibited by unlabelled IGFBP-3 at high doses (10 mu g/ml) and reduced but not a bolished by preincubation of I-125-IGFBP-3 with excess IGF-I. Digestio n of I-125-IGFBP-3 with mature CPA produced a 26 kDa product. Modifica tion of IGFBP-3 by CPA or binding to proCPA may provide a mechanism fo r modulation of IGFBP activity and hence IGF action.