ABSTRACT
Plasminogen activator inhibitor (PAI)-2 expression is acutely upregulated in pregnancy, inflammation, infection, and other pathophysiological conditions. Circumstances that prevent PAI-2 upregulation are associated with chronic pathology. Altogether this strongly suggests that PAI-2 is one of the many proteins that maintain homeostasis during damage or stress. However, several functions ranging from a classical serpin to various intracellular roles have been ascribed to PAI-2 and, because none of these have been definitively proven in vivo, to this day its precise role or roles remains an enigma. This review readdresses the evidence supporting a role for PAI-2 in fibrinolysis and proteolysis within extracellular environments and includes a review of the many potential intracellular functions attributed to PAI-2.
KEYWORDS
PAI-2 - SERPINB2 - proteolysis - fibrinolysis - extracellular - intracellular
REFERENCES
-
1
Kawano T, Morimoto K, Uemura Y.
Partial purification and properties of urokinase inhibitor from human placenta.
J Biochem.
1970;
67
(3)
333-342
-
2
Astedt B, Lecander I, Brodin T, Lundblad A, Löw K.
Purification of a specific placental plasminogen activator inhibitor by monoclonal antibody and its complex formation with plasminogen activator.
Thromb Haemost.
1985;
53
(1)
122-125
-
3
Astedt B, Bladh B, Christensen U, Lecander I.
Different inhibition of one and two chain tissue plasminogen activator by a placental inhibitor studied with two tripeptide-p-nitroanilide substrates.
Scand J Clin Lab Invest.
1985;
45
(5)
429-435
-
4
Thorsen S, Philips M, Selmer J, Lecander I, Astedt B.
Kinetics of inhibition of tissue-type and urokinase-type plasminogen activator by plasminogen-activator inhibitor type 1 and type 2.
Eur J Biochem.
1988;
175
(1)
33-39
-
5
Loskutoff D J, Edgington T E.
Synthesis of a fibrinolytic activator and inhibitor by endothelial cells.
Proc Natl Acad Sci U S A.
1977;
74
(9)
3903-3907
-
6
Kruithof E K, Baker M S, Bunn C L.
Biological and clinical aspects of plasminogen activator inhibitor type 2.
Blood.
1995;
86
(11)
4007-4024
-
7
Kruithof E K, Tran-Thang C, Ransijn A, Bachmann F.
Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma.
Blood.
1984;
64
(4)
907-913
-
8
Silverman G A, Bird P I, Carrell R W et al..
The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature.
J Biol Chem.
2001;
276
(36)
33293-33296
-
9
Law R H, Zhang Q, McGowan S et al..
An overview of the serpin superfamily.
Genome Biol.
2006;
7
(5)
216
-
10
Kruithof E K, Vassalli J D, Schleuning W D, Mattaliano R J, Bachmann F.
Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937.
J Biol Chem.
1986;
261
(24)
11207-11213
-
11
Genton C, Kruithof E K, Schleuning W D.
Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells.
J Cell Biol.
1987;
104
(3)
705-712
-
12
Antalis T M, La Linn M, Donnan K et al..
The serine proteinase inhibitor (serpin) plasminogen activation inhibitor type 2 protects against viral cytopathic effects by constitutive interferon alpha/beta priming.
J Exp Med.
1998;
187
(11)
1799-1811
-
13
Dickinson J L, Bates E J, Ferrante A, Antalis T M.
Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor alpha-induced apoptosis. Evidence for an alternate biological function.
J Biol Chem.
1995;
270
(46)
27894-27904
-
14
Dickinson J L, Norris B J, Jensen P H, Antalis T M.
The C-D interhelical domain of the serpin plasminogen activator inhibitor-type 2 is required for protection from TNF-alpha induced apoptosis.
Cell Death Differ.
1998;
5
(2)
163-171
-
15
Fish R J, Kruithof E K.
Evidence for serpinB2-independent protection from TNF-alpha-induced apoptosis.
Exp Cell Res.
2006;
312
(3)
350-361
-
16
Croucher D, Ranson M, Saunders D.
SerpinB2.
In: UCSD nature molecule pages 1.0. In press
-
17
Medcalf R L, Stasinopoulos S J.
The undecided serpin. The ins and outs of plasminogen activator inhibitor type 2.
FEBS J.
2005;
272
(19)
4858-4867
-
18
Croucher D R, Saunders D N, Lobov S, Ranson M.
Revisiting the biological roles of PAI2 (SERPINB2) in cancer.
Nat Rev Cancer.
2008;
8
(7)
535-545
-
19
Ye R D, Ahern S M, Le Beau M M, Lebo R V, Sadler J E.
Structure of the gene for human plasminogen activator inhibitor-2. The nearest mammalian homologue of chicken ovalbumin.
J Biol Chem.
1989;
264
(10)
5495-5502
-
20
Remold-O'Donnell E.
The ovalbumin family of serpin proteins.
FEBS Lett.
1993;
315
(2)
105-108
-
21
Scott F L, Eyre H J, Lioumi M et al..
Human ovalbumin serpin evolution: phylogenic analysis, gene organization, and identification of new PI8-related genes suggest that two interchromosomal and several intrachromosomal duplications generated the gene clusters at 18q21-q23 and 6p25.
Genomics.
1999;
62
(3)
490-499
-
22
Lobov S, Wilczynska M, Bergström F, Johansson L B, Ny T.
Structural bases of the redox-dependent conformational switch in the serpin PAI-2.
J Mol Biol.
2004;
344
(5)
1359-1368
-
23
Wohlwend A, Belin D, Vassalli J D.
Plasminogen activator-specific inhibitors produced by human monocytes/macrophages.
J Exp Med.
1987;
165
(2)
320-339
-
24
Hamilton J A, Whitty G A, Stanton H et al..
Macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor stimulate the synthesis of plasminogen-activator inhibitors by human monocytes.
Blood.
1993;
82
(12)
3616-3621
-
25
Ritchie H, Jamieson A, Booth N A.
Regulation, location and activity of plasminogen activator inhibitor 2 (PAI-2) in peripheral blood monocytes, macrophages and foam cells.
Thromb Haemost.
1997;
77
(6)
1168-1173
-
26
Swartz J M, Byström J, Dyer K D, Nitto T, Wynn T A, Rosenberg H F.
Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes.
J Leukoc Biol.
2004;
76
(4)
812-819
-
27
Robinson N A, Lapic S, Welter J F, Eckert R L.
S100A11, S100A10, annexin I, desmosomal proteins, small proline-rich proteins, plasminogen activator inhibitor-2, and involucrin are components of the cornified envelope of cultured human epidermal keratinocytes.
J Biol Chem.
1997;
272
(18)
12035-12046
-
28
Akiyama H, Ikeda K, Kondo H, Kato M, McGeer P L.
Microglia express the type 2 plasminogen activator inhibitor in the brain of control subjects and patients with Alzheimer's disease.
Neurosci Lett.
1993;
164
(1–2)
233-235
-
29
Kruithof E K, Tran-Thang C, Gudinchet A et al..
Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors.
Blood.
1987;
69
(2)
460-466
-
30
Ritchie H, Booth N A.
The distribution of the secreted and intracellular forms of plasminogen activator inhibitor 2 (PAI-2) in human peripheral blood monocytes is modulated by serum.
Thromb Haemost.
1998;
79
(4)
813-817
-
31
Gettins P GW.
Serpin structure, mechanism, and function.
Chem Rev.
2002;
102
(12)
4751-4804
-
32
Huntington J A.
Shape-shifting serpins—advantages of a mobile mechanism.
Trends Biochem Sci.
2006;
31
(8)
427-435
-
33
Schwartz B S.
Differential inhibition of soluble and cell surface receptor-bound single-chain urokinase by plasminogen activator inhibitor type 2. A potential regulatory mechanism.
J Biol Chem.
1994;
269
(11)
8319-8323
-
34
Wojta J, Hoover R L, Daniel T O.
Vascular origin determines plasminogen activator expression in human endothelial cells. Renal endothelial cells produce large amounts of single chain urokinase type plasminogen activator.
J Biol Chem.
1989;
264
(5)
2846-2852
-
35
Leung K C, Byatt J A, Stephens R W.
The resistance of fibrin-stimulated tissue plasminogen activator to inactivation by a class PAI-2 inhibitor (minactivin).
Thromb Res.
1987;
46
(6)
755-766
-
36
Ritchie H, Lawrie L C, Mosesson M W, Booth N A.
Characterization of crosslinking sites in fibrinogen for plasminogen activator inhibitor 2 (PAI-2).
Ann N Y Acad Sci.
2001;
936
215-218
-
37
Leung K C, Byatt J A, Stephens R W.
Poly-D-lysine dependent inactivation of tissue plasminogen activator by a class PAI-2 inhibitor (minactivin).
Thromb Res.
1987;
46
(6)
767-777
-
38
Lobov S, Croucher D R, Saunders D N, Ranson M.
Plasminogen activator inhibitor type 2 inhibits cell surface associated tissue plasminogen activator in vitro: potential receptor interactions.
Thromb Haemost.
2008;
100
(2)
319-329
-
39
Lee J A, Croucher D R, Ranson M.
Differential endocytosis of tissue plasminogen activator by serpins PAI-1 and PAI-2 on human peripheral blood monocytes.
Thromb Haemost.
2010;
104
(6)
1133-1142
-
40
Al-Ejeh F, Croucher D, Ranson M.
Kinetic analysis of plasminogen activator inhibitor type-2: urokinase complex formation and subsequent internalisation by carcinoma cell lines.
Exp Cell Res.
2004;
297
(1)
259-271
-
41
Lecander I, Astedt B.
Specific plasminogen activator inhibitor of placental type PAI 2 occurring in amniotic fluid and cord blood.
J Lab Clin Med.
1987;
110
(5)
602-605
-
42
Astedt B, Lindoff C, Lecander I.
Significance of the plasminogen activator inhibitor of placental type (PAI-2) in pregnancy.
Semin Thromb Hemost.
1998;
24
(5)
431-435
-
43
Booth N A, Reith A, Bennett B.
A plasminogen activator inhibitor (PAI-2) circulates in two molecular forms during pregnancy.
Thromb Haemost.
1988;
59
(1)
77-79
-
44
Kinnby B.
The plasminogen activating system in periodontal health and disease.
Biol Chem.
2002;
383
(1)
85-92
-
45
Virtanen O J, Sirén V, Multanen J et al..
Plasminogen activators and their inhibitors in human saliva and salivary gland tissue.
Eur J Oral Sci.
2006;
114
(1)
22-26
-
46
Scott-Coombes D, Whawell S, Vipond M N, Thompson J.
Human intraperitoneal fibrinolytic response to elective surgery.
Br J Surg.
1995;
82
(3)
414-417
-
47
Alemán C, Alegre J, Monasterio J et al..
Association between inflammatory mediators and the fibrinolysis system in infectious pleural effusions.
Clin Sci (Lond).
2003;
105
(5)
601-607
-
48
Csutak A, Silver D M, Tozsér J et al..
Plasminogen activator inhibitor in human tears after laser refractive surgery.
J Cataract Refract Surg.
2008;
34
(6)
897-901
-
49
Scherrer A, Kruithof E K, Grob J P.
Plasminogen activator inhibitor-2 in patients with monocytic leukemia.
Leukemia.
1991;
5
(6)
479-486
-
50
Robbie L A, Dummer S, Booth N A, Adey G D, Bennett B.
Plasminogen activator inhibitor 2 and urokinase-type plasminogen activator in plasma and leucocytes in patients with severe sepsis.
Br J Haematol.
2000;
109
(2)
342-348
-
51
Lecander I, Martinsson G, Casslén B et al..
Occurrence of the specific plasminogen activator inhibitor of placental type, PAI-2 in ascitic fluid and tumour vessel blood from patients with ovarian carcinoma.
Fibrinolysis.
1990;
4
(4)
221-224
-
52
Varro A, Hemers E, Archer D et al..
Identification of plasminogen activator inhibitor-2 as a gastrin-regulated gene: role of Rho GTPase and menin.
Gastroenterology.
2002;
123
(1)
271-280
-
53
Coolman M, de Groot C J, Steegers E A et al..
Concentrations of plasminogen activators and their inhibitors in blood preconceptionally, during and after pregnancy.
Eur J Obstet Gynecol Reprod Biol.
2006;
128
(1-2)
22-28
-
54
Hunt B J, Missfelder-Lobos H, Parra-Cordero M et al..
Pregnancy outcome and fibrinolytic, endothelial and coagulation markers in women undergoing uterine artery Doppler screening at 23 weeks.
J Thromb Haemost.
2009;
7
(6)
955-961
-
55
Brenner B.
Haemostatic changes in pregnancy.
Thromb Res.
2004;
114
(5–6)
409-414
-
56
Reith A, Booth N A, Moore N R, Cruickshank D J, Bennett B.
Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, pre-eclampsia and hydatidiform mole.
Br J Obstet Gynaecol.
1993;
100
(4)
370-374
-
57
Kiso U, Henschen A, Bohn H et al..
Identity between the placental protein PP10 and the specific plasminogen activator inhibitor of placental type PAI-2.
Biochim Biophys Acta.
1991;
1074
(1)
74-78
-
58
Nakashima A, Kobayashi T, Terao T.
Fibrinolysis during normal pregnancy and severe preeclampsia relationships between plasma levels of plasminogen activators and inhibitors.
Gynecol Obstet Invest.
1996;
42
(2)
95-101
-
59
Brown J M, Watanabe K, Cohen R L, Chambers D A.
Molecular characterization of plasminogen activators in human gingival crevicular fluid.
Arch Oral Biol.
1995;
40
(9)
839-845
-
60
Yin X, Bunn C L, Bartold P M.
Detection of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2(PAI-2) in gingival crevicular fluid from healthy, gingivitis and periodontitis patients.
J Clin Periodontol.
2000;
27
(3)
149-156
-
61
Saunders D N, Buttigieg K M, Gould A, McPhun V, Baker M S.
Immunological detection of conformational neoepitopes associated with the serpin activity of plasminogen activator inhibitor type-2.
J Biol Chem.
1998;
273
(18)
10965-10971
-
62
Lindberg P, Baker M S, Kinnby B.
The localization of the relaxed form of plasminogen activator inhibitor type 2 in human gingival tissues.
Histochem Cell Biol.
2001;
116
(5)
447-452
-
63
Baker M S, Green S P, Goss N, Katrantzis M, Doe W F.
Plasminogen activator inhibitor 2 (PAI-2) is not inactivated by exposure to oxidants which can be released from activated neutrophils.
Biochem Biophys Res Commun.
1990;
166
(2)
993-1000
-
64
Bouchet C, Hacène K, Martin P M et al..
Dissemination risk index based on plasminogen activator system components in primary breast cancer.
J Clin Oncol.
1999;
17
(10)
3048-3057
-
65
Foekens J A, Peters H A, Look M P et al..
The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients.
Cancer Res.
2000;
60
(3)
636-643
-
66
Pedersen A N, Brünner N, Høyer-Hansen G et al..
Determination of the complex between urokinase and its type-1 inhibitor in plasma from healthy donors and breast cancer patients.
Clin Chem.
1999;
45
(8 Pt 1)
1206-1213
-
67
Sten-Linder M, Seddighzadeh M, Engel G et al..
Prognostic importance of the uPa/PAI-1 complex in breast cancer.
Anticancer Res.
2001;
21
(4B)
2861-2865
-
68
Zhang S J, Zou M, Lu L et al..
Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity.
PLoS Genet.
2009;
5
(8)
e1000604
-
69
Byström J, Wynn T A, Domachowske J B, Rosenberg H F.
Gene microarray analysis reveals interleukin-5-dependent transcriptional targets in mouse bone marrow.
Blood.
2004;
103
(3)
868-877
-
70
Park J M, Greten F R, Wong A et al..
Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis—CREB and NF-kappaB as key regulators.
Immunity.
2005;
23
(3)
319-329
-
71
Greten F R, Arkan M C, Bollrath J et al..
NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta.
Cell.
2007;
130
(5)
918-931
-
72
Sekine H, Mimura J, Oshima M et al..
Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock.
Mol Cell Biol.
2009;
29
(24)
6391-6400
-
73
Jensen P H, Fladmark K E, Gjertsen B T, Vintermyr O K.
Caspase I-related protease inhibition retards the execution of okadaic acid- and camptothecin-induced apoptosis and PAI-2 cleavage, but not commitment to cell death in HL-60 cells.
Br J Cancer.
1999;
79
(11-12)
1685-1691
-
74
Schroder W A, Le T T, Major L et al..
A physiological function of inflammation-associated SerpinB2 is regulation of adaptive immunity.
J Immunol.
2010;
184
(5)
2663-2670
-
75
Krishnamurti C, Wahl L M, Alving B M.
Stimulation of plasminogen activator inhibitor activity in human monocytes infected with dengue virus.
Am J Trop Med Hyg.
1989;
40
(1)
102-107
-
76
Krishnamurti C, Alving B.
Effect of dengue virus on procoagulant and fibrinolytic activities of monocytes.
Rev Infect Dis.
1989;
11
(Suppl 4)
S843-S846
-
77
Losick V P, Isberg R R.
NF-kappaB translocation prevents host cell death after low-dose challenge by Legionella pneumophila
.
J Exp Med.
2006;
203
(9)
2177-2189
-
78
Haile W B, Coleman J L, Benach J L.
Reciprocal upregulation of urokinase plasminogen activator and its inhibitor, PAI-2, by Borrelia burgdorferi affects bacterial penetration and host-inflammatory response.
Cell Microbiol.
2006;
8
(8)
1349-1360
-
79
Gan H, Newman G W, Remold H G.
Plasminogen activator inhibitor type 2 prevents programmed cell death of human macrophages infected with Mycobacterium avium, serovar 4.
J Immunol.
1995;
155
(3)
1304-1315
-
80
Loeffler J, Haddad Z, Bonin M et al..
Interaction analyses of human monocytes co-cultured with different forms of Aspergillus fumigatus.
.
J Med Microbiol.
2009;
58
(Pt 1)
49-58
-
81
Silverman G A, Jockel J I, Domer P H, Mohr R M, Taillon-Miller P, Korsmeyer S J.
Yeast artificial chromosome cloning of a two-megabase-size contig within chromosomal band 18q21 establishes physical linkage between BCL2 and plasminogen activator inhibitor type-2.
Genomics.
1991;
9
(2)
219-228
-
82
Jensen P H, Cressey L I, Gjertsen B T et al..
Cleaved intracellular plasminogen activator inhibitor 2 in human myeloleukaemia cells is a marker of apoptosis.
Br J Cancer.
1994;
70
(5)
834-840
-
83
Zhou H M, Bolon I, Nichols A, Wohlwend A, Vassalli J D.
Overexpression of plasminogen activator inhibitor type 2 in basal keratinocytes enhances papilloma formation in transgenic mice.
Cancer Res.
2001;
61
(3)
970-976
-
84
Zhang Y Q, Li P, Hou M et al..
Identification of interaction between PAI-2 and IRF-3.
Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai).
2003;
35
(7)
661-665
-
85
Fan J, Zhang Y Q, Li P et al..
Interaction of plasminogen activator inhibitor-2 and proteasome subunit, beta type 1.
Acta Biochim Biophys Sin (Shanghai).
2004;
36
(1)
42-46
-
86
Jensen P H, Jensen T G, Laug W E, Hager H, Gliemann J, Pepinsky B.
The exon 3 encoded sequence of the intracellular serine proteinase inhibitor plasminogen activator inhibitor 2 is a protein binding domain.
J Biol Chem.
1996;
271
(43)
26892-26899
-
87
Jensen P H, Schüler E, Woodrow G et al..
A unique interhelical insertion in plasminogen activator inhibitor-2 contains three glutamines, Gln83, Gln84, Gln86, essential for transglutaminase-mediated cross-linking.
J Biol Chem.
1994;
269
(21)
15394-15398
-
88
Ritchie H, Robbie L A, Kinghorn S, Exley R, Booth N A.
Monocyte plasminogen activator inhibitor 2 (PAI-2) inhibits u-PA-mediated fibrin clot lysis and is cross-linked to fibrin.
Thromb Haemost.
1999;
81
(1)
96-103
-
89
Mikus P, Ny T.
Intracellular polymerization of the serpin plasminogen activator inhibitor type 2.
J Biol Chem.
1996;
271
(17)
10048-10053
-
90
Wilczynska M, Lobov S, Ohlsson P I, Ny T.
A redox-sensitive loop regulates plasminogen activator inhibitor type 2 (PAI-2) polymerization.
EMBO J.
2003;
22
(8)
1753-1761
-
91
Darnell G A, Antalis T M, Johnstone R W et al..
Inhibition of retinoblastoma protein degradation by interaction with the serpin plasminogen activator inhibitor 2 via a novel consensus motif.
Mol Cell Biol.
2003;
23
(18)
6520-6532
-
92
Darnell G A, Antalis T M, Rose B R, Suhrbier A.
Silencing of integrated human papillomavirus type 18 oncogene transcription in cells expressing SerpinB2.
J Virol.
2005;
79
(7)
4246-4256
-
93
Syrjänen S, Naud P, Sarian L et al..
Up-regulation of plasminogen activator inhibitor-2 is associated with high-risk HPV and grade of cervical lesion at baseline but does not predict outcomes of high-risk HPV infections or incident CIN.
Am J Clin Pathol.
2009;
132
(6)
883-892
-
94
Darnell G A, Schroder W A, Gardner J et al..
SerpinB2 is an inducible host factor involved in enhancing HIV-1 transcription and replication.
J Biol Chem.
2006;
281
(42)
31348-31358
-
95
Mikus P, Urano T, Liljeström P, Ny T.
Plasminogen-activator inhibitor type 2 (PAI-2) is a spontaneously polymerising SERPIN. Biochemical characterisation of the recombinant intracellular and extracellular forms.
Eur J Biochem.
1993;
218
(3)
1071-1082
-
96
Wilczynska M, Lobov S, Ny T.
The spontaneous polymerization of plasminogen activator inhibitor type-2 and Z-antitrypsin are due to different molecular aberrations.
FEBS Lett.
2003;
537
(1–3)
11-16
-
97
Stein P E, Carrell R W.
What do dysfunctional serpins tell us about molecular mobility and disease?.
Nat Struct Biol.
1995;
2
(2)
96-113
-
98
Davis R L, Shrimpton A E, Holohan P D et al..
Familial dementia caused by polymerization of mutant neuroserpin.
Nature.
1999;
401
(6751)
376-379
-
99
Whisstock J C, Bottomley S P.
Structural biology: Serpins' mystery solved.
Nature.
2008;
455
(7217)
1189-1190
-
100
Almeida-Vega S, Catlow K, Kenny S, Dimaline R, Varro A.
Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1.
Am J Physiol Gastrointest Liver Physiol.
2009;
296
(2)
G414-G423
-
101
Cousin E, Medcalf R L, Bergonzelli G E, Kruithof E K.
Regulatory elements involved in constitutive and phorbol ester-inducible expression of the plasminogen activator inhibitor type 2 gene promoter.
Nucleic Acids Res.
1991;
19
(14)
3881-3886
-
102
Mahony D, Kalionis B, Antalis T M.
Plasminogen activator inhibitor type-2 (PAI-2) gene transcription requires a novel NF-kappaB-like transcriptional regulatory motif.
Eur J Biochem.
1999;
263
(3)
765-772
-
103
Schuster W A, Medcalf R L, Kruithof E KO.
Localization and characterisation of a retinoic acid response-like element in the plasminogen activator inhibitor-2 gene promoter.
Fibrinolysis.
1994;
8
113-119
-
104
Schuster W A, Medcalf R L, Kruithof E K.
Retinoic acid potentiates phorbol ester-mediated induction of urokinase and plasminogen activator inhibitor type 2 in human myeloid leukemic cell lines.
Endocrinology.
1993;
133
(4)
1724-1730
-
105
Sutter T R, Guzman K, Dold K M, Greenlee W F.
Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleukin-1 beta.
Science.
1991;
254
(5030)
415-418
-
106
Antalis T M, Costelloe E, Muddiman J, Ogbourne S, Donnan K.
Regulation of the plasminogen activator inhibitor type-2 gene in monocytes: localization of an upstream transcriptional silencer.
Blood.
1996;
88
(10)
3686-3697
-
107
Dear A E, Shen Y, Rüegg M, Medcalf R L.
Molecular mechanisms governing tumor-necrosis-factor-mediated regulation of plasminogen-activator inhibitor type-2 gene expression.
Eur J Biochem.
1996;
241
(1)
93-100
-
108
Ogbourne S M, Antalis T M.
Characterisation of PAUSE-1, a powerful silencer in the human plasminogen activator inhibitor type 2 gene promoter.
Nucleic Acids Res.
2001;
29
(19)
3919-3927
-
109
Maurer F, Tierney M, Medcalf R L.
An AU-rich sequence in the 3′-UTR of plasminogen activator inhibitor type 2 (PAI-2) mRNA promotes PAI-2 mRNA decay and provides a binding site for nuclear HuR.
Nucleic Acids Res.
1999;
27
(7)
1664-1673
-
110
Maurer F, Medcalf R L.
Plasminogen activator inhibitor type 2 gene induction by tumor necrosis factor and phorbol ester involves transcriptional and post-transcriptional events. Identification of a functional nonameric AU-rich motif in the 3′-untranslated region.
J Biol Chem.
1996;
271
(42)
26074-26080
-
111
Yu H, Stasinopoulos S, Leedman P, Medcalf R L.
Inherent instability of plasminogen activator inhibitor type 2 mRNA is regulated by tristetraprolin.
J Biol Chem.
2003;
278
(16)
13912-13918
-
112
Tierney M J, Medcalf R L.
Plasminogen activator inhibitor type 2 contains mRNA instability elements within exon 4 of the coding region. Sequence homology to coding region instability determinants in other mRNAs.
J Biol Chem.
2001;
276
(17)
13675-13684
-
113
Dougherty K M, Pearson J M, Yang A Y, Westrick R J, Baker M S, Ginsburg D.
The plasminogen activator inhibitor-2 gene is not required for normal murine development or survival.
Proc Natl Acad Sci U S A.
1999;
96
(2)
686-691
-
114
Ong K, Horsfall W, Conway E M, Schuh A C.
Early embryonic expression of murine coagulation system components.
Thromb Haemost.
2000;
84
(6)
1023-1030
-
115
Antalis T M, Clark M A, Barnes T et al..
Cloning and expression of a cDNA coding for a human monocyte-derived plasminogen activator inhibitor.
Proc Natl Acad Sci U S A.
1988;
85
(4)
985-989
-
116
van den Berg E A, le Clercq E, Kooistra T, Frants R R, Bakker E.
The human gene for plasminogen activator inhibitor 2 (PAI2) exhibits an EcoRI RFLP.
Nucleic Acids Res.
1990;
18
(9)
2837
-
117
Palafox-Sánchez C A, Vázquez-Del Mercado M, Orozco-Barocio G et al..
A functional Ser(413)/Ser(413) PAI-2 polymorphism is associated with susceptibility and damage index score in systemic lupus erythematosus.
Clin Appl Thromb Hemost.
2009;
15
(2)
233-238
-
118
Vázquez-Del Mercado M, García-Cobian T A, Muñoz Valle J F et al..
Genotype Ser413/Ser of PAI-2 polymorphism Ser413/Cys is associated with anti-phospholipid syndrome and systemic lupus erythematosus in a familial case: comparison with healthy controls.
Scand J Rheumatol.
2007;
36
(3)
206-210
-
119
Buyru N, Altinisik J, Gurel C B, Ulutin T.
PCR-RFLP detection of PAI-2 variants in myocardial infarction.
Clin Appl Thromb Hemost.
2003;
9
(4)
333-336
-
120
McCarthy J J, Parker A, Salem R GeneQuest Investigators et al.
Large scale association analysis for identification of genes underlying premature coronary heart disease: cumulative perspective from analysis of 111 candidate genes.
J Med Genet.
2004;
41
(5)
334-341
-
121
Foy C A, Grant P J.
PCR-RFLP detection of PAI-2 gene variants: prevalence in ethnic groups and disease relationship in patients undergoing coronary angiography.
Thromb Haemost.
1997;
77
(5)
955-958
-
122
Shioji G, Ezura Y, Nakajima T et al..
Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer.
J Hum Genet.
2005;
50
(10)
507-515
-
123
Gibson C S, MacLennan A H, Dekker G A et al..
Genetic polymorphisms and spontaneous preterm birth.
Obstet Gynecol.
2007;
109
(2 Pt 1)
384-391
-
124
Di Bernardo M C, Matakidou A, Eisen T, Houlston R S. GELCAPS Consortium .
Plasminogen activator inhibitor variants PAI-1 A15T and PAI-2 S413C influence lung cancer prognosis.
Lung Cancer.
2009;
65
(2)
237-241
-
125
Ellis V, Wun T C, Behrendt N, Rønne E, Danø K.
Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors.
J Biol Chem.
1990;
265
(17)
9904-9908
-
126
Medcalf R L, Kruithof E K, Schleuning W D.
Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin-responsive genes.
J Exp Med.
1988;
168
(2)
751-759
-
127
Pytel B A, Peppel K, Baglioni C.
Plasminogen activator inhibitor type-2 is a major protein induced in human fibroblasts and SK-MEL-109 melanoma cells by tumor necrosis factor.
J Cell Physiol.
1990;
144
(3)
416-422
-
128
Gyetko M R, Shollenberger S B, Sitrin R G.
Urokinase expression in mononuclear phagocytes: cytokine-specific modulation by interferon-gamma and tumor necrosis factor-alpha.
J Leukoc Biol.
1992;
51
(3)
256-263
-
129
Jang W G, Kim H S, Park K G et al..
Analysis of proteome and transcriptome of tumor necrosis factor alpha stimulated vascular smooth muscle cells with or without alpha lipoic acid.
Proteomics.
2004;
4
(11)
3383-3393
-
130
Wang Y, Jensen P J.
Regulation of the level and glycosylation state of plasminogen activator inhibitor type 2 during human keratinocyte differentiation.
Differentiation.
1998;
63
(2)
93-99
-
131
Champelovier P, Simon A, Garrel C, Levacher G, Praloran V, Seigneurin D.
Is interferon gamma one key of metastatic potential increase in human bladder carcinoma?.
Clin Cancer Res.
2003;
9
(12)
4562-4569
-
132
Hannocks M J, Oliver L, Gabrilove J L, Wilson E L.
Regulation of proteolytic activity in human bone marrow stromal cells by basic fibroblast growth factor, interleukin-1, and transforming growth factor beta.
Blood.
1992;
79
(5)
1178-1184
-
133
Gyetko M R, Wilkinson C C, Sitrin R G.
Monocyte urokinase expression: modulation by interleukins.
J Leukoc Biol.
1993;
53
(5)
598-601
-
134
Hamilton J A, Wojta J, Gallichio M, McGrath K, Filonzi E L.
Contrasting effects of transforming growth factor-beta and IL-1 on the regulation of plasminogen activator inhibitors in human synovial fibroblasts.
J Immunol.
1993;
151
(10)
5154-5161
-
135
Woodruff P G, Boushey H A, Dolganov G M et al..
Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids.
Proc Natl Acad Sci U S A.
2007;
104
(40)
15858-15863
-
136
George F, Pourreau-Schneider N, Arnoux D et al..
Modulation of tPA, PAI-1 and PAI-2 antigen and mRNA levels by EGF in the A431 cell line.
Blood Coagul Fibrinolysis.
1990;
1
(6)
689-693
-
137
Piquette G N, Crabtree M E, el-Danasouri I, Milki A, Polan M L.
Regulation of plasminogen activator inhibitor-1 and -2 messenger ribonucleic acid levels in human cumulus and granulosa-luteal cells.
J Clin Endocrinol Metab.
1993;
76
(2)
518-523
-
138
Medcalf R L, Van den Berg E, Schleuning W D.
Glucocorticoid-modulated gene expression of tissue- and urinary-type plasminogen activator and plasminogen activator inhibitor 1 and 2.
J Cell Biol.
1988;
106
(3)
971-978
-
139
Schwartz B S, Bradshaw J D.
Regulation of plasminogen activator inhibitor mRNA levels in lipopolysaccharide-stimulated human monocytes. Correlation with production of the protein.
J Biol Chem.
1992;
267
(10)
7089-7094
-
140
Costelloe E O, Stacey K J, Antalis T M, Hume D A.
Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin.
J Leukoc Biol.
1999;
66
(1)
172-182
-
141
Suzuki T, Hashimoto S, Toyoda N et al..
Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE.
Blood.
2000;
96
(7)
2584-2591
-
142
Xiao Y, Bartold P M.
Modulating effect of serum on the stimulation of plasminogen activator inhibitor 2 production in human gingival fibroblasts by lipopolysaccharide and interleukin-1beta.
J Int Acad Periodontol.
2004;
6
(3)
81-88
-
143
Niiya K, Taniguchi T, Shinbo M et al..
Different regulation of plasminogen activator inhibitor 2 gene expression by phorbol ester and cAMP in human myeloid leukemia cell line PL-21.
Thromb Haemost.
1994;
72
(1)
92-97
-
144
Seo E Y, Piao Y J, Kim J S, Suhr K B, Park J K, Lee J H.
Identification of calcium-induced genes in HaCaT keratinocytes by polymerase chain reaction-based subtractive hybridization.
Arch Dermatol Res.
2002;
294
(9)
411-418
-
145
Ahn N S, Hu H, Park J S et al..
Molecular mechanisms of the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced inverted U-shaped dose responsiveness in anchorage independent growth and cell proliferation of human breast epithelial cells with stem cell characteristics.
Mutat Res.
2005;
579
(1–2)
189-199
-
146
Sharon R, Abramovitz R, Miskin R.
Plasminogen mRNA induction in the mouse brain after kainate excitation: codistribution with plasminogen activator inhibitor-2 (PAI-2) mRNA.
Brain Res Mol Brain Res.
2002;
104
(2)
170-175
-
147
Medcalf R L.
Cell- and gene-specific interactions between signal transduction pathways revealed by okadaic acid. Studies on the plasminogen activating system.
J Biol Chem.
1992;
267
(17)
12220-12226
-
148
Dear A E, Medcalf R L.
The novel anti-tumour agent oxamflatin differentially regulates urokinase and plasminogen activator inhibitor type 2 expression and inhibits urokinase-mediated proteolytic activity.
Biochim Biophys Acta.
2000;
1492
(1)
15-22
-
149
Schleuning W D, Medcalf R L, Hession C, Rothenbühler R, Shaw A, Kruithof E K.
Plasminogen activator inhibitor 2: regulation of gene transcription during phorbol ester-mediated differentiation of U-937 human histiocytic lymphoma cells.
Mol Cell Biol.
1987;
7
(12)
4564-4567
-
150
Feener E P, Northrup J M, Aiello L P, King G L.
Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells.
J Clin Invest.
1995;
95
(3)
1353-1362
-
151
Hamaguchi M, Morishita Y, Takahashi I, Ogura M, Takamatsu J, Saito H.
FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line.
Blood.
1991;
77
(1)
94-100
-
152
Camerer E, Gjernes E, Wiiger M, Pringle S, Prydz H.
Binding of factor VIIa to tissue factor on keratinocytes induces gene expression.
J Biol Chem.
2000;
275
(9)
6580-6585
-
153
Ritchie H, Jamieson A, Booth N A.
Thrombin modulates synthesis of plasminogen activator inhibitor type 2 by human peripheral blood monocytes.
Blood.
1995;
86
(9)
3428-3435
-
154
Lundgren C H, Sawa H, Sobel B E, Fujii S.
Modulation of expression of monocyte/macrophage plasminogen activator activity and its implications for attenuation of vasculopathy.
Circulation.
1994;
90
(4)
1927-1934
-
155
Buechler C, Ullrich H, Ritter M et al..
Lipoprotein (a) up-regulates the expression of the plasminogen activator inhibitor 2 in human blood monocytes.
Blood.
2001;
97
(4)
981-986
-
156
Braungart E, Magdolen V, Degitz K.
Retinoic acid upregulates the plasminogen activator system in human epidermal keratinocytes.
J Invest Dermatol.
2001;
116
(5)
778-784
-
157
Montemurro P, Barbuti G, Conese M et al..
Retinoic acid stimulates plasminogen activator inhibitor 2 production by blood mononuclear cells and inhibits urokinase-induced extracellular proteolysis.
Br J Haematol.
1999;
107
(2)
294-299
-
158
Wada H, Kaneko T, Wakita Y et al..
Effect of lipoproteins on tissue factor activity and PAI-II antigen in human monocytes and macrophages.
Int J Cardiol.
1994;
47
(1, Suppl)
S21-S25
-
159
Jankova L, Harrop S J, Saunders D N et al..
Crystal structure of the complex of plasminogen activator inhibitor 2 with a peptide mimicking the reactive center loop.
J Biol Chem.
2001;
276
(46)
43374-43382
-
160 DeLano W L. The PyMOL Molecular Graphics System. San Carlos, CA: DeLano Scientific; 2002
Marie RansonPh.D.
School of Biological Sciences, University of Wollongong, Northfields Avenue
Wollongong NSW 2522, Australia
Email: mranson@uow.edu.au
