Abstract
Apart from tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), a third PA appears to occur in human plasma. Its activity is initiated when appropriate triggers of the contact system are added, and the activation depends on the presence of factor XII and prekallikrein in plasma. The activity of this, so-called, contact-system dependent PA accounts for 30% of the PA activity in the dextran sulphate euglobulin fraction of plasma and was shown not to be an intrinsic property of one of the contact-system components, nor could it be inhibited by inhibitory antibodies against t-PA or u-PA. We have succeeded in identifying this third PA in dextran sulphate euglobulin fractions of human plasma. Its smallest unit (SDS-PAGE) is an inactive 110 kDa single-chain polypeptide which upon activation of the contact system is converted to a cleaved, disulphide-bridged molecule with PA activity. The native form, presumably, is an oligomer, since the apparent Mr on gel-chromatography is 600,000. The IEP is 4.8, much lower than that of t-PA and u-PA. Although the active 110 kDa polypeptide cannot be inhibited by anti-u-PA, it yet comprises a 37 kDa piece with some u-PA related antigenic determinants. However, these determinants are in a latent or cryptic form, only detectable after denaturation by SDS. The 110 kDa polypeptide is evidently not a dimer of 55 kDa u-PA or a complex of u-PA with an inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
| Original language | English |
|---|---|
| Pages (from-to) | 390-397 |
| Journal | Thrombosis and haemostasis |
| Volume | 64 |
| Issue number | 3 |
| Publication status | Published - 30 Nov 1990 |
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Keywords
- Antibodies
- Blotting, Western
- Electrophoresis, Polyacrylamide Gel
- Enzyme Precursors
- Humans
- Immunoassay
- Kallikreins
- Plasminogen Activators
- Prekallikrein
- Urokinase-Type Plasminogen Activator
- Research Support, Non-U.S. Gov't
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The contact-system dependent plasminogen activator from human plasma : identification and characterization. / Binnema, D J; Dooijewaard, G; van Iersel, J J; Turion, P N; Kluft, C.
In: Thrombosis and haemostasis, Vol. 64, No. 3, 30.11.1990, p. 390-397.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - The contact-system dependent plasminogen activator from human plasma
T2 - identification and characterization
AU - Binnema, D J
AU - Dooijewaard, G
AU - van Iersel, J J
AU - Turion, P N
AU - Kluft, C
PY - 1990/11/30
Y1 - 1990/11/30
N2 - Apart from tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), a third PA appears to occur in human plasma. Its activity is initiated when appropriate triggers of the contact system are added, and the activation depends on the presence of factor XII and prekallikrein in plasma. The activity of this, so-called, contact-system dependent PA accounts for 30% of the PA activity in the dextran sulphate euglobulin fraction of plasma and was shown not to be an intrinsic property of one of the contact-system components, nor could it be inhibited by inhibitory antibodies against t-PA or u-PA. We have succeeded in identifying this third PA in dextran sulphate euglobulin fractions of human plasma. Its smallest unit (SDS-PAGE) is an inactive 110 kDa single-chain polypeptide which upon activation of the contact system is converted to a cleaved, disulphide-bridged molecule with PA activity. The native form, presumably, is an oligomer, since the apparent Mr on gel-chromatography is 600,000. The IEP is 4.8, much lower than that of t-PA and u-PA. Although the active 110 kDa polypeptide cannot be inhibited by anti-u-PA, it yet comprises a 37 kDa piece with some u-PA related antigenic determinants. However, these determinants are in a latent or cryptic form, only detectable after denaturation by SDS. The 110 kDa polypeptide is evidently not a dimer of 55 kDa u-PA or a complex of u-PA with an inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
AB - Apart from tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), a third PA appears to occur in human plasma. Its activity is initiated when appropriate triggers of the contact system are added, and the activation depends on the presence of factor XII and prekallikrein in plasma. The activity of this, so-called, contact-system dependent PA accounts for 30% of the PA activity in the dextran sulphate euglobulin fraction of plasma and was shown not to be an intrinsic property of one of the contact-system components, nor could it be inhibited by inhibitory antibodies against t-PA or u-PA. We have succeeded in identifying this third PA in dextran sulphate euglobulin fractions of human plasma. Its smallest unit (SDS-PAGE) is an inactive 110 kDa single-chain polypeptide which upon activation of the contact system is converted to a cleaved, disulphide-bridged molecule with PA activity. The native form, presumably, is an oligomer, since the apparent Mr on gel-chromatography is 600,000. The IEP is 4.8, much lower than that of t-PA and u-PA. Although the active 110 kDa polypeptide cannot be inhibited by anti-u-PA, it yet comprises a 37 kDa piece with some u-PA related antigenic determinants. However, these determinants are in a latent or cryptic form, only detectable after denaturation by SDS. The 110 kDa polypeptide is evidently not a dimer of 55 kDa u-PA or a complex of u-PA with an inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
KW - Antibodies
KW - Blotting, Western
KW - Electrophoresis, Polyacrylamide Gel
KW - Enzyme Precursors
KW - Humans
KW - Immunoassay
KW - Kallikreins
KW - Plasminogen Activators
KW - Prekallikrein
KW - Urokinase-Type Plasminogen Activator
KW - Research Support, Non-U.S. Gov't
M3 - Article
C2 - 2128968
VL - 64
SP - 390
EP - 397
JO - Thrombosis and haemostasis
JF - Thrombosis and haemostasis
SN - 0340-6245
IS - 3
ER -