Protease nexins

Protease nexin (From cultured human fibroblasts) [148263-58-5], Purified by affinity binding of protease nexin to dextran sulfate-Sepharose. [Farrell et al. Biochem J 237 707 1986.]... 

Scott R. W., Eaton D. L., Duran N., Baker J. B. Regulation of extracellular plasminogen activator by human fibroblasts. The role of protease nexin. J Biol Chem 1983 258,4397-403. 

Van Nostrand W. E Schmaier A. H., Farrow J. S., Cunningham D. D. Protease nexin-0 (amyloid (3-protein precursor) A platelet a granule protein. Science 1990 248,745-8. 

Baker J. B Low D. A., Simmer R. L. Protease nexin A cellular component that links thrombin and plasminogen activator and mediates their binding to cells. Cell 1980 21, 37-45. 

Another serine protease inhibitor of the al-antitrypsin family (serpin) is heparin cofactor II (HCII), which also forms a 1 1 complex with thrombin, but does not react with factor Xa [4,10]. The rate of inhibition of thrombin is not only increased by heparinoids but also by the related glycosaminoglycan dermatan sulfate. The identification of an inhibitor variant and site-directed mutagenesis studies on HC II cDNA led to the understanding that the binding sites for heparin and dermatan sulfate may be overlapping but not identical. Further proteinase inhibitors interacting with heparinoids are tissue factor pathway inhibitor and protease nexin-1. 

Protease nexin 2 is identical to the secreted form of the amyloid precursor protein containing the Kunitz-type serine protease inhibitor domain (128,129), Protease nexin 2 circulates in blood stored as a platelet a-granule protein, which is secreted upon platelet activation (127). Protease nexin 2 inhibits trypsin- and chymotrypsin-like serine proteases and is also a potent inhibitor of factor Xla (126,127,128). Its location in platelets and its ability to inhibit factor Xla suggests a role in regulating blood coagulation for protease nexin 2. 

Eaton DL, Baker JB. Evidence that a variety of cultured cells secrete protease nexin and produce a distinct cytoplasmic serine protease-binding factor. J Cell Physiol 1983 I 17 175-182. 

Since aiAT represents the archetype for the serpin (serine-proteinase inhibitor) superfamily of proteins, it is possible that similar oxidative or proteolytic mechanisms may function in the inactivation of other serpins that are important in controlling the inflammatory cascade. Some serpins contain a readily oxidised reactive-centre methionine residue (e.g. plasminogen activator-inhibitor [108] and a2-antiplasmin [109]), whilst all serpins (including antithrombin III [110] and protease nexin I [111]) contain an exposed loop which is susceptible to cleavage by proteinases. 

The two platelet membrane glycoproteins for which the strongest evidence exists at the present time that they are thrombin receptors are a specific form of the GPIb-DC-V conq>lex and PARI, the protease-activated thrombin receptor these will be discussed next in this review. Based on their apparent ability to form complexes with a hrombin, several other proteins had previously t en proposed as thrombin receptors but in only a few cases were the necessary further studies carried out to test these hypotheses. Protease nexin 1 was proposed as a thrombin receptor based on the similar time courses of complex formation and platelet activation but it was subsequently found that protease nexin 1 cannot be a receptor since it is an internal conq>onent of platelets that is expressed on the surface only ater activation. Glycoprotein V has also been proposed as a thrombin receptor based on the feet that it can be cleaved by low concentrations of a-thrombin but subsequent studies (reviewed in ) showed that there was no consistent relationship between the rate or extent of GPV hydrolysis and the extent of platelet activation induced by a-thrombin. Another thrombin-activatable receptor, PAW, has been identified in mouse platelets but not in human platelets using a reverse transcriptase/ polymerase chain reaction approach (unpublished data and S.Coughlin, personal communication). PAR3 has, however, been reported cloned from a human platelet cDNA library. ... 

Rossignol, P., Ho-Tin-Noe, B., Vranckx, R., et al., Protease-nexin-1 inhibits plasminogen activation-induced apoptosis of adherent cells. J. Biol. Chem. 279, 10346-10356 (2004). 

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