Plasminogen activator inhibitor-2 (placental PAI), a serine protease inhibitor of the serpin superfamily, is a coagulation factor that inactivates tPA and urokinase. It is present in most cells, especially monocytes/macrophages. PAI-2 exists in two forms, a 60-kDa extracellular glycosylated form and a 43-kDa intracellular form.
It is present only at detectable quantities in blood during pregnancy, as it is produced by the placenta, and may explain partially the increased rate of thrombosis during pregnancy. The majority of expressed PAI-2 remains unsecreted due to the presence of an inefficient internal signal peptide.
Plasminogen activator inhibitor-2 (SerpinB2) has been reported to bind a series of intracellular and extracellular proteins. Whether SerpinB2's physiological function is inhibition of the extracellular protease urokinase and/or whether SerpinB2 has intracellular activities remains controversial. At least one of SerpinB2's physiological functions may involve regulation of adaptive immunity.[1]
Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J (1992). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis. 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID1286667.
Ellis V, Wun TC, Behrendt N, Rønne E, Danø K (1990). "Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors". J. Biol. Chem. 265 (17): 9904–8. PMID2161846.
Samia JA, Alexander SJ, Horton KW, Auron PE, Byers MG, Shows TB, Webb AC (1990). "Chromosomal organization and localization of the human urokinase inhibitor gene: perfect structural conservation with ovalbumin". Genomics. 6 (1): 159–67. doi:10.1016/0888-7543(90)90461-3. PMID2303256.
Schwartz BS, Monroe MC, Bradshaw JD (1989). "Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X". Blood. 73 (8): 2188–95. PMID2471561.
Ye RD, Ahern SM, Le Beau MM, Lebo RV, Sadler JE (1989). "Structure of the gene for human plasminogen activator inhibitor-2. The nearest mammalian homologue of chicken ovalbumin". J. Biol. Chem. 264 (10): 5495–502. PMID2494165.
Laug WE, Aebersold R, Jong A, Rideout W, Bergman BL, Baker J (1989). "Isolation of multiple types of plasminogen activator inhibitors from vascular smooth muscle cells". Thromb. Haemost. 61 (3): 517–21. PMID2799763.
Kruithof EK, Cousin E (1988). "Plasminogen activator inhibitor 2. Isolation and characterization of the promoter region of the gene". Biochem. Biophys. Res. Commun. 156 (1): 383–8. doi:10.1016/S0006-291X(88)80852-0. PMID2845977.
Ye RD, Wun TC, Sadler JE (1987). "cDNA cloning and expression in Escherichia coli of a plasminogen activator inhibitor from human placenta". J. Biol. Chem. 262 (8): 3718–25. PMID3029122.
Dickinson JL, Bates EJ, Ferrante A, Antalis TM (1995). "Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor alpha-induced apoptosis. Evidence for an alternate biological function". J. Biol. Chem. 270 (46): 27894–904. doi:10.1074/jbc.270.46.27894. PMID7499264.
Mikus P, Urano T, Liljeström P, Ny T (1993). "Plasminogen-activator inhibitor type 2 (PAI-2) is a spontaneously polymerising SERPIN. Biochemical characterisation of the recombinant intracellular and extracellular forms". Eur. J. Biochem. 218 (3): 1071–82. doi:10.1111/j.1432-1033.1993.tb18467.x. PMID7506655.
Jensen PJ, Wu Q, Janowitz P, Ando Y, Schechter NM (1995). "Plasminogen activator inhibitor type 2: an intracellular keratinocyte differentiation product that is incorporated into the cornified envelope". Exp. Cell Res. 217 (1): 65–71. doi:10.1006/excr.1995.1064. PMID7867722.
Akiyama H, Ikeda K, Kondo H, Kato M, McGeer PL (1993). "Microglia express the type 2 plasminogen activator inhibitor in the brain of control subjects and patients with Alzheimer's disease". Neurosci. Lett. 164 (1–2): 233–5. doi:10.1016/0304-3940(93)90899-V. PMID8152607.
Ragno P, Montuori N, Vassalli JD, Rossi G (1993). "Processing of complex between urokinase and its type-2 inhibitor on the cell surface. A possible regulatory mechanism of urokinase activity". FEBS Lett. 323 (3): 279–84. doi:10.1016/0014-5793(93)81357-6. PMID8388810.
Bartuski AJ, Kamachi Y, Schick C, Overhauser J, Silverman GA (1997). "Cytoplasmic antiproteinase 2 (PI8) and bomapin (PI10) map to the serpin cluster at 18q21.3". Genomics. 43 (3): 321–8. doi:10.1006/geno.1997.4827. PMID9268635.
Mahony D, Stringer BW, Dickinson JL, Antalis TM (1998). "DNase I hypersensitive sites in the 5' flanking region of the human plasminogen activator inhibitor type 2 (PAI-2) gene are associated with basal and tumor necrosis factor-alpha-induced transcription in monocytes". Eur. J. Biochem. 256 (3): 550–9. doi:10.1046/j.1432-1327.1998.2560550.x. PMID9780231.
Nishida Y, Hayashi Y, Imai Y, Itoh H (1998). "Expression and localization of the urokinase-type plasminogen activator receptor (uPAR) in the human placenta". Kobe J Med Sci. 44 (1): 31–43. PMID9846056.