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Gene Review

SERPINB2  -  serpin peptidase inhibitor, clade B...

Homo sapiens

Synonyms: HsT1201, Monocyte Arg-serpin, PAI, PAI-2, PAI2, ...
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Disease relevance of SERPINB2

  • Clinical groups consisting of pregnant women with either severe preeclampsia or chronic hypertension with superimposed severe preeclampsia, as well as normal pregnant and nonpregnant women, were analyzed in a panel of functional and immunologic assays for PAI-1 and PAI-2 [1].
  • In contrast, PAI-2 levels were reduced in preeclamptic patients with infarction in comparison with those of patients without infarction (141 ng/mL v 212.9 ng/mL) [1].
  • The patients with chronic hypertension and superimposed severe preeclampsia exhibited PAI-2 levels comparable to those of the pure preeclamptic group, whereas their antigenic and functional PAI-1 levels were intermediate (94 ng/mL and 3.25 U/mL, respectively) between the normal pregnant and the pure preeclamptic groups [1].
  • However, only PAI-2 reduced the incidence of lung and brain metastasis following liver gene transfer [2].
  • Neither PAI-1 nor PAI-2 could be detected in Bowes melanoma cells or in a renal adenocarcinoma cell line (ACHN), while the histiocytic lymphoma cell (U-937) produced only PAI-2 [3].

Psychiatry related information on SERPINB2

  • Localization of type 2 plasminogen activator inhibitor (PAI-2) was investigated immunohistochemically in postmortem brain tissue of control subjects and patients with Alzheimer's disease (AD) [4].
  • After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function [5].
  • In the first study, 226 women were administered the Personality Assessment Inventory, borderline scales (PAI-BOR; L.C. Morey, The Personality Assessment Inventory, Professional Manual, 1991) and a questionnaire that assessed time in menstrual cycle and use of oral contraceptives, that is synthetic estrogens [6].
  • RESULTS: Physical activity index (PAI = 24 h EE/SMR) on day 1 (part 1) was 1.55 +/- 0.04, close to the predicted value of 1.5, but between-subject variation was large (range: 1.39-1.68) [7].
  • We classified a sample of criminal defendants as high, moderate, or low in psychopathy, based on PCL-R scores, and compared their scores on indices typically used to detect malingering on the MMPI-2, the PAI and the SIRS [8].

High impact information on SERPINB2

  • The serine proteinase inhibitor (serpin) plasminogen activator inhibitor type 2 (PAI-2) is well characterized as an inhibitor of extracellular urokinase-type plasminogen activator [9].
  • This protection did not appear to be related to an effect on apoptosis but was associated with a PAI-2-mediated induction of constitutive low-level interferon (IFN)-alpha/beta production and IFN-stimulated gene factor 3 (ISGF3) activation, which primed the cells for rapid induction of antiviral genes [9].
  • PAI-2 was also induced in macrophages in response to viral RNA suggesting that PAI-2 is a virus response gene [9].
  • This primed phenotype was associated with a rapid development of resistance to infection by the PAI-2 transfected cells and the establishment of a persistent productive infection [9].
  • These observations, together with the recently demonstrated PAI-2-mediated inhibition of tumor necrosis factor-alpha induced apoptosis, (a) illustrate that PAI-2 has an additional and distinct function as an intracellular regulator of signal transduction pathway(s) and (b) demonstrate a novel activity for a eukaryotic serpin [9].

Chemical compound and disease context of SERPINB2

  • Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin [10].
  • This inhibition was not due to cellular toxicity, the phospholipidlike nature of lipid X, interference with the PAI-2 assay, or monocyte production of a substance interfering with PAI-2 [11].
  • Both PAI and procoagulant factors play an important role in the pathophysiology of inflammation, DIC, and ischemia [12].
  • The 214 patients showing significant coronary artery stenosis (greater than 50% reduction of luminal area in any of the great coronary arteries) had higher mean levels of tPA (P less than 0.001) and PAI (P less than 0.01) than a random population sample of similar age [13].
  • Oral HRT use was associated with increased plasma levels of Factor IX, activated protein C (APC) resistance, and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity [14].

Biological context of SERPINB2

  • Furthermore, the interaction of ch-uPA(RRHR) with PAI-2 was also substantially enhanced, while the interaction with other members of the serine proteinase inhibitor superfamily, protein nexin 1, alpha1-PI, and C1-inhibitor, was unaffected indicating that the RRHR motif is not a general serine proteinase inhibitor binding site [15].
  • During early puerperium of both normal pregnant women and patients, plasma PAI-1 antigen and activity decreased within one day to approximately the levels detected in normal nonpregnant women, while PAI-2 levels remained elevated for over 11 days [1].
  • In amniotic fluid, PAI-1 antigen levels increased from 194 +/- 109 ng/ml (first trimester) to 640 +/- 396 ng/ml (third trimester) and PAI-2 antigen levels increased from 72 +/- 57 ng/ml to 173 +/- 97 ng/ml [16].
  • The role of PAI-2 in the inhibition of peritoneal fibrinolysis during inflammation was investigated in this study [17].
  • The effect of cervical dilatation on PA and PAI concentrations was compared in a laminaria tent group and a mechanical dilatation (control) group [18].

Anatomical context of SERPINB2

  • Cytoplasmic and nuclear interaction between Rb family proteins and PAI-2: a physiological crosstalk in human corneal and conjunctival epithelial cells [19].
  • In the present study we have characterized a novel PAI-2-specific ELISA, designed to measure PAI-2 antigen levels in tumor cytosols [20].
  • Stimulation of U937 cells with phorbol 12-myristate 13-acetate was accompanied by a further reduction in receptor-bound uPA inhibition by PAI-1 and PAI-2 to 1.7 x 10(6) and 1.1 x 10(5) M-1 s-1, respectively [21].
  • In contrast, preincubation of the amnion membrane with PAI-2 which does not bind to the extracellular matrix has no effect on monocyte invasiveness [22].
  • However, RA potentiated PMA-mediated induction of PAI-2 mRNA in HL-60 and U937 cells and PAI-2 antigen in all four cell lines [23].

Associations of SERPINB2 with chemical compounds


Physical interactions of SERPINB2

  • In contrast to the active enzyme, the uPA/PAI-2 complex is rapidly cleared from the monocyte cell surface; this involves an initial cleavage of the complex at the cell surface, followed by endocytosis and degradation [28].
  • These data suggest that the predominant form of PAI-2 in placenta extract is heterogeneous and of high molecular mass, containing complexes in which vitronectin is covalently bound to PAI-2 by disulfide bridges [29].
  • PAI-2 could bind PRPF8 C-terminal in both the inside and outside of nuclear [30].
  • This finding suggested that PAI-2 formed a complex with a target proteinase, which could be involved in mediating the cytolytic activity of TNF [31].

Enzymatic interactions of SERPINB2


Regulatory relationships of SERPINB2

  • Our results indicate that components of the plasminogen activation cascade are up-regulated in endometrial cancer and suggest the role of PAI-2 in determining invasive potential of endometrial carcinomas [34].
  • The production of large amounts of PAI-2 may represent an additional control mechanism of proteinase activity [35].
  • In contrast, Glu158-scu-PA bound to u-PA receptors on monocytes was only minimally inhibited by a large molar excess of PAI-2 [36].
  • In contrast, TNF alpha-induced expression of PAI-2 was synergistically increased by addition of IFN-gamma [37].
  • THP-1 cells expressing active PAI-2 also displayed an altered phenotype in response to phorbol ester-induced differentiation that was concomitant with a reduction in CD14 expression [38].

Other interactions of SERPINB2

  • This was the result of an increase of PAI-1 antigen; PAI-2 antigen was not detectable [39].
  • We speculate that PAI-2 may serve as an inhibitor for uPA in human primary breast cancers [20].
  • Here, we show that pRb2/p130 and Rb1/p105, but not p107, interact with PAI-2 in both the cytoplasm and nucleus of normal primary human corneal and conjunctival epithelial cells [19].
  • At variance with the former, which was largely released in the culture medium, PAI-2 was mainly cell-associated. t-PA antigen was found in all but two cell lines while u-PA antigen was detected in relatively high concentrations in 8 cell lines [35].
  • Inhibition of HPMC fibrinolytic activity is due, in part, to elaboration of plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) as well as antiplasmins [25].

Analytical, diagnostic and therapeutic context of SERPINB2


  1. Changes in the plasma levels of type 1 and type 2 plasminogen activator inhibitors in normal pregnancy and in patients with severe preeclampsia. Estellés, A., Gilabert, J., Aznar, J., Loskutoff, D.J., Schleef, R.R. Blood (1989) [Pubmed]
  2. Reduction of tumor cell migration and metastasis by adenoviral gene transfer of plasminogen activator inhibitors. Praus, M., Wauterickx, K., Collen, D., Gerard, R.D. Gene Ther. (1999) [Pubmed]
  3. Detection of both type 1 and type 2 plasminogen activator inhibitors in human cells. Schleef, R.R., Wagner, N.V., Loskutoff, D.J. J. Cell. Physiol. (1988) [Pubmed]
  4. Microglia express the type 2 plasminogen activator inhibitor in the brain of control subjects and patients with Alzheimer's disease. Akiyama, H., Ikeda, K., Kondo, H., Kato, M., McGeer, P.L. Neurosci. Lett. (1993) [Pubmed]
  5. Effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator and plasminogen activator inhibitor. Veenstra, J., Kluft, C., Ockhuizen, T.H., vd Pol, H., Wedel, M., Schaafsma, G. Thromb. Haemost. (1990) [Pubmed]
  6. Estrogen fluctuations, oral contraceptives and borderline personality. DeSoto, M.C., Geary, D.C., Hoard, M.K., Sheldon, M.S., Cooper, L. Psychoneuroendocrinology (2003) [Pubmed]
  7. Energy balance in a respiration chamber: individual adjustment of energy intake to energy expenditure. Schrauwen, P., van Marken Lichtenbelt, W.D., Westerterp, K.R. Int. J. Obes. Relat. Metab. Disord. (1997) [Pubmed]
  8. Psychopathy and malingering of psychiatric disorder in criminal defendants. Kucharski, L.T., Duncan, S., Egan, S.S., Falkenbach, D.M. Behavioral sciences & the law. (2006) [Pubmed]
  9. The serine proteinase inhibitor (serpin) plasminogen activation inhibitor type 2 protects against viral cytopathic effects by constitutive interferon alpha/beta priming. Antalis, T.M., La Linn, M., Donnan, K., Mateo, L., Gardner, J., Dickinson, J.L., Buttigieg, K., Suhrbier, A. J. Exp. Med. (1998) [Pubmed]
  10. Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6. Marutsuka, K., Hasui, Y., Asada, Y., Naito, S., Osada, Y., Sumiyoshi, A. Clin. Exp. Metastasis (1995) [Pubmed]
  11. Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X. Schwartz, B.S., Monroe, M.C., Bradshaw, J.D. Blood (1989) [Pubmed]
  12. Defibrotide reduces monocyte PAI-2 and procoagulant activity. Abbate, R., Gori, A.M., Martini, F., Attanasio, M., Comeglio, P., Giusti, B., Zarone, N., Francalanci, I., Prisco, D., Gensini, G.F. Semin. Thromb. Hemost. (1995) [Pubmed]
  13. Evidence for increased levels of plasminogen activator inhibitor and tissue plasminogen activator in plasma of patients with angiographically verified coronary artery disease. Olofsson, B.O., Dahlén, G., Nilsson, T.K. Eur. Heart J. (1989) [Pubmed]
  14. Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional population survey. Lowe, G.D., Upton, M.N., Rumley, A., McConnachie, A., O'Reilly, D.S., Watt, G.C. Thromb. Haemost. (2001) [Pubmed]
  15. Introduction of an RRHR motif into chicken urokinase-type plasminogen activator (ch-uPA) confers sensitivity to plasminogen activator inhibitor (PAI)-1 and PAI-2 and allows ch-uPA-mediated extracellular matrix degradation to be controlled by PAI-1. Sipley, J.D., Alexander, D.S., Testa, J.E., Quigley, J.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  16. Plasminogen activator inhibitors type 1 and type 2 and plasminogen activators in amniotic fluid during pregnancy. Estellés, A., Gilabert, J., Andrés, C., España, F., Aznar, J. Thromb. Haemost. (1990) [Pubmed]
  17. Plasminogen activator inhibitor 2 reduces peritoneal fibrinolytic activity in inflammation. Whawell, S.A., Vipond, M.N., Scott-Coombes, D.M., Thompson, J.N. The British journal of surgery. (1993) [Pubmed]
  18. Placental and decidual u-PA, t-PA, PAI-1 and PAI-2 concentrations, as affected by cervical dilatation with laminaria tents or Hegar dilators. Jonasson, A., Larsson, B., Lecander, I., Astedt, B. Thromb. Res. (1989) [Pubmed]
  19. Cytoplasmic and nuclear interaction between Rb family proteins and PAI-2: a physiological crosstalk in human corneal and conjunctival epithelial cells. Macaluso, M., Montanari, M., Marshall, C.M., Gambone, A.J., Tosi, G.M., Giordano, A., Massaro-Giordano, M. Cell Death Differ. (2006) [Pubmed]
  20. Plasminogen activator inhibitor-2: prognostic relevance in 1012 patients with primary breast cancer. Foekens, J.A., Buessecker, F., Peters, H.A., Krainick, U., van Putten, W.L., Look, M.P., Klijn, J.G., Kramer, M.D. Cancer Res. (1995) [Pubmed]
  21. Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors. Ellis, V., Wun, T.C., Behrendt, N., Rønne, E., Danø, K. J. Biol. Chem. (1990) [Pubmed]
  22. Matrix-bound plasminogen activator inhibitor type 1 inhibits the invasion of human monocytes into interstitial tissue. Kirchheimer, J.C., Binder, B.R., Remold, H.G. J. Immunol. (1990) [Pubmed]
  23. Retinoic acid potentiates phorbol ester-mediated induction of urokinase and plasminogen activator inhibitor type 2 in human myeloid leukemic cell lines. Schuster, W.A., Medcalf, R.L., Kruithof, E.K. Endocrinology (1993) [Pubmed]
  24. Isolation of multiple types of plasminogen activator inhibitors from vascular smooth muscle cells. Laug, W.E., Aebersold, R., Jong, A., Rideout, W., Bergman, B.L., Baker, J. Thromb. Haemost. (1989) [Pubmed]
  25. Pathways of fibrin turnover of human pleural mesothelial cells in vitro. Idell, S., Zwieb, C., Kumar, A., Koenig, K.B., Johnson, A.R. Am. J. Respir. Cell Mol. Biol. (1992) [Pubmed]
  26. Inhibitors of the protease domain of urokinase-type plasminogen activator. Rockway, T.W., Nienaber, V., Giranda, V.L. Curr. Pharm. Des. (2002) [Pubmed]
  27. Poly-D-lysine dependent inactivation of tissue plasminogen activator by a class PAI-2 inhibitor (minactivin). Leung, K.C., Byatt, J.A., Stephens, R.W. Thromb. Res. (1987) [Pubmed]
  28. The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes. Estreicher, A., Mühlhauser, J., Carpentier, J.L., Orci, L., Vassalli, J.D. J. Cell Biol. (1990) [Pubmed]
  29. Isolation of plasminogen activator inhibitor-2 (PAI-2) from human placenta. Evidence for vitronectin/PAI-2 complexes in human placenta extract. Radtke, K.P., Wenz, K.H., Heimburger, N. Biol. Chem. Hoppe-Seyler (1990) [Pubmed]
  30. Interaction between plasminogen activator inhibitor type-2 and pre-mRNA processing factor 8. Fan, J., Zhang, Y.Q., Li, P., Tong, C., Tan, L., Zhu, Y.S. Acta Biochim. Biophys. Sin. (Shanghai) (2004) [Pubmed]
  31. Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type-2. Kumar, S., Baglioni, C. J. Biol. Chem. (1991) [Pubmed]
  32. A unique interhelical insertion in plasminogen activator inhibitor-2 contains three glutamines, Gln83, Gln84, Gln86, essential for transglutaminase-mediated cross-linking. Jensen, P.H., Schüler, E., Woodrow, G., Richardson, M., Goss, N., Højrup, P., Petersen, T.E., Rasmussen, L.K. J. Biol. Chem. (1994) [Pubmed]
  33. Evidence for intracellular cleavage of plasminogen activator inhibitor type 2 (PAI-2) in normal epidermal keratinocytes. Risse, B.C., Chung, N.M., Baker, M.S., Jensen, P.J. J. Cell. Physiol. (2000) [Pubmed]
  34. Plasminogen activator inhibitor type 2: potential prognostic factor for endometrial carcinomas. Osmak, M., Babić, D., Abramić, M., Milicić, D., Vrhovec, I., Skrk, J. Neoplasma (2001) [Pubmed]
  35. Cultured human mesangial cells produce both type 1 and type 2 plasminogen activator inhibitors. Colucci, M., Gesualdo, L., Montemurro, P., Cavallo, L.G., Conese, M., Mascolo, E., Ranieri, E., Di Paolo, S., Schena, F.P., Semeraro, N. Thromb. Haemost. (1995) [Pubmed]
  36. Differential inhibition of soluble and cell surface receptor-bound single-chain urokinase by plasminogen activator inhibitor type 2. A potential regulatory mechanism. Schwartz, B.S. J. Biol. Chem. (1994) [Pubmed]
  37. Interferon-gamma modulates the fibrinolytic response in cultured human endothelial cells. Arnman, V., Stemme, S., Rymo, L., Risberg, B. Thromb. Res. (1995) [Pubmed]
  38. Plasminogen activator inhibitor type 2: a regulator of monocyte proliferation and differentiation. Yu, H., Maurer, F., Medcalf, R.L. Blood (2002) [Pubmed]
  39. Progress of fibrinolysis during tumor necrosis factor infusions in humans. Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type-1, and fibrin(ogen) degradation products. van Hinsbergh, V.W., Bauer, K.A., Kooistra, T., Kluft, C., Dooijewaard, G., Sherman, M.L., Nieuwenhuizen, W. Blood (1990) [Pubmed]
  40. Plasminogen activator inhibitor type-2 in the lesional epidermis of lupus erythematosus. Bechtel, M.J., Schaefer, B.M., Kramer, M.D. Br. J. Dermatol. (1996) [Pubmed]
  41. Localization and distribution of tissue type and urokinase type plasminogen activators and their inhibitors Type 1 and 2 in human and rhesus monkey fetal membranes. Liu, Y.X., Hu, Z.Y., Liu, K., Byrne, S., Zou, R.J., Ny, T., d'Lacey, C., Ockleford, C.D. Placenta (1998) [Pubmed]
  42. Independent regulation of plasminogen activator inhibitor 2 and plasminogen activator inhibitor 1 in human synovial fibroblasts. Hamilton, J.A., Cheung, D., Filonzi, E.L., Piccoli, D.S., Wojta, J., Gallichio, M., McGrath, K., Last, K. Arthritis Rheum. (1992) [Pubmed]
  43. Effects of cellular transformation on expression of plasminogen activator inhibitors 1 and 2. Evidence for independent regulation. Cohen, R.L., Niclas, J., Lee, W.M., Wun, T.C., Crowley, C.W., Levinson, A.D., Sadler, J.E., Shuman, M.A. J. Biol. Chem. (1989) [Pubmed]
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