Structure of the Human Protease Nexin Gene and Expression of Recombinant Forms of PN-I

Protease nexin (PN-I) is a member of the serpin family of serine protease inhibitors that are characterized by the formation of an irreversible complex with the catalytic site of their target serine proteases.1 PN-I is known to inhibit a number of biologically relevant serine proteases such as thrombin, urokinase, plasmin, and plasminogen activators.2–4 The significance of regulatory inhibitors in controlling the activity of the serine proteases has only begun to be appreciated in the areas of cell movement, blood coagulation, fibrinolysis, extracellular matrix modulation, and mitosis.5–8 Recently PN-I has been shown to be identical to glial derived nexin, which has been reported to possess neurite extension activity on peripheral nerve cells 3,9–11 Native PN-I is a glycoprotein of approximately 45,000 daltons that is secreted by various fibroblasts and extravascular cells.12 Multiple forms of PN-I have been described which differ in their behavior on SDS-PAGE, pH gradient gels, and heparin affinity chromatography.4’13 Although glycosylation differences can most certainly account for some of these differences, we have identified two species of human PN-I which we have designated αPN-I and βPN-I that differ by a net change of three amino acids.14