Abstract:
:Binding of the coagulation protease factor VIIa to its receptor Tissue Factor (TF) induces intracellular signals in several cell types including HaCaT keratinocytes. TF belongs to the cytokine receptor family, but is most likely not alone in transferring the complete TF/FVIIa signal over the plasma membrane. The protease activated receptor PAR2 is involved in factor VIIa and factor Xa signal transduction. Our results indicate that the epidermal growth factor receptor (EGFR) and the proline rich tyrosine kinase 2 (PYK2) participate in TF/FVIIa signalling as formation of the TF/FVIIa complex increased the phosphorylation of these proteins. Both FVIIa protease activity and available TF were necessary for generation of the signal. Increased tyrosine phosphorylation of the EGFR was observed following TF/FVIIa complex formation on the cell surface. The EGFR kinase inhibitor tyrphostin AG1478 abrogated the TF/FVIIa-complex induced MAP kinase activation and mRNA increase of egr-1, heparin-binding EGF, and interleukin-8 following FVIIa addition. Using specific antibodies, increased phosphorylation of PYK2 tyrosine residues 402 and 580 was observed. The first site is the major autophosphorylation site and the docking site for Src family kinases. The second site is important for the kinase activity. The Src family kinase Yes and the tyrosine phosphatase SHP-2 were detected in immunoprecipitates using either anti-PYK2 or anti-EGFR antibodies. Their coprecipitation with EGFR increased in the presence of FVIIa. Moreover, the coprecipitation of EGFR and PYK2 increased with FVIIa stimulation. Together, these data suggest that EGFR, PYK2, Yes, and SHP-2 are involved in transduction of the TF/FVIIa signal possibly via transactivation of the EGF receptor.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Wiiger MT,Prydz Hdoi
10.1160/TH03-08-0549keywords:
subject
Has Abstractpub_date
2004-07-01 00:00:00pages
13-22issue
1eissn
0340-6245issn
2567-689Xpii
04070013journal_volume
92pub_type
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journal_title:Thrombosis and haemostasis
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abstract::The efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well-documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combi...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::We have investigated the influence of long term oral anticoagulants (OAC) upon the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-Dimer in 20 patients affected by a proximal deep vein thrombosis (DVT) diagnosed by ultrasonic duplex scanning. Patients (63 +/-...
journal_title:Thrombosis and haemostasis
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更新日期:1993-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/th07-05-0377
更新日期:2007-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:1981-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH07-08-0484
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH15-12-0982
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
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更新日期:2005-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-1692721
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-09-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2009-06-01 00:00:00
abstract::Glucose intolerance, hyperinsulinaemia, dyslipoproteinaemia and multiple disturbances of haemostatic function are characteristics of young men with premature coronary artery disease. The relations between glucose, insulin and insulin propeptides, in the fasting state, and after an oral glucose load, and haemostatic fu...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-05-01 00:00:00
abstract::Thirty-one non-hemophilic patients with acquired antibodies to factor VIII were entered into a prospective, randomized, multi-institutional trial to determine the safety and efficacy of prednisone (P), cyclophosphamide (C), or the combination in the treatment of this disorder. Patients were eligible if they had antibo...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1993-11-15 00:00:00
abstract::Antithrombin (AT) activity tests are used for diagnosing hereditary AT deficiency, a main genetic determinant of thrombophilia. They are either based on inhibition of thrombin (FIIa) or activated factor X (FXa). FXa-based assays have been suggested to be preferable to FIIa-based assays due to their higher sensitivity ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH17-08-0568
更新日期:2018-02-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-04-30 00:00:00
abstract::Activated protein C (APC) is a serine proteinase that regulates blood coagulation. In plasma it is inhibited mainly by the protein C inhibitor (PCI). The plasma concentrations of APC-PCI complex is increased in hypercoagulative states such as deep venous thrombosis. Formation of the APC-PCI complex induces a drastic c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00