Dennis D. Cunningham

Regulation of Protease Nexin-1 Activity by Heparin and Heparan Sulfate

Protease nexin-1 (PN-1) is a 43 kDa protease inhibitor that is synthesized and released by a variety of cultured cells including fibroblasts, smooth muscle cells, astrocytes and to a lesser extent, neurons (1–4). It is not present at significant concentrations in plasma, although it is found in platelets and is released upon platelet activation (5,6). PN-1 inhibits certain serine proteases by forming a complex with their catalytic site serine residue. The complexes then bind back to the cells, via a receptor for the PN-1 moiety of the complex, and are rapidly internalized and degraded. This provides a mechanism for inhibiting and clearing these proteases from the extracellular environment (7).