Juri Koschelnik - Academia.edu (original) (raw)
Papers by Juri Koschelnik
Fibrinolysis and Proteolysis, 1998
This review focuses on signal transduction via the urokinase receptor, a very controversial issue... more This review focuses on signal transduction via the urokinase receptor, a very controversial issue. It describes data on membrane and extracellular matrix proteins interacting with this receptor, phosphorylation events induced by activation of the receptor, and influence of receptor activation on gene regulation and biologic functions of various cells. Due to the use of many different cells and culture conditions by different authors, and their focus on specific events within signaling cascades, a conclusive pathway of signal transduction via the urokinase receptor is still lacking. Actually this receptor seems to modify different signaling pathways used by integrins or cytokines rather than activate a signaling pathway of its own.
The FASEB Journal, 2001
The aim of this study was to investigate whether 8-iso-PGF 2α , a nonenzymatic free radical-induc... more The aim of this study was to investigate whether 8-iso-PGF 2α , a nonenzymatic free radical-induced oxidation product of arachidonic acid, activates endothelial cells (EC) to bind monocytes, which is a key initiating event in atherogenesis. Since thromboxane induces leukocyte adhesion ...
Journal of Biological Chemistry, 2002
In this study we have investigated the role of a specific corepressor of EGR-1, NAB2, to down-reg... more In this study we have investigated the role of a specific corepressor of EGR-1, NAB2, to down-regulate vascular endothelial growth factor (VEGF)-induced gene expression in endothelial cells and to inhibit angiogenesis. Firstly, we show a reciprocal regulation of EGR-1 and NAB2 following VEGF treatment. During the initial phase EGR-1 is rapidly induced and NAB2 levels are down-regulated. This is followed by a reduction of EGR-1 and a concomitant increase of NAB2. Secondly, using the tissue factor gene as a readout for VEGFinduced and EGR-1-regulated gene expression we demonstrate that NAB2 can completely block VEGF-induced tissue factor reporter gene activity. Thirdly, by adenovirus-mediated expression we show that NAB2 inhibits up-regulation of tissue factor, VEGF receptor-1, and urokinase plasminogen activator mRNAs even when a combination of VEGF and bFGF is used for induction. In addition, NAB2 overexpression significantly reduced tubule and sprout formation in two different in vitro angiogenesis assays and largely prevented the invasion of cells and formation of vessel-like structures in the murine Matrigel model. These data suggest that NAB2 regulation represents a mechanism to guarantee transient EGR-1 activity following exposure of endothelial cells to VEGF and that NAB2 overexpression could be used to inhibit signals involved in the early phase of angiogenesis.
Circulation, 2002
Background — To investigate the contribution of inflammation to postangioplasty lumen loss, we us... more Background — To investigate the contribution of inflammation to postangioplasty lumen loss, we used an adenoviral gene therapy approach to inhibit the central inflammatory mediator nuclear factor-κB (NF-κB) by overexpression of its natural inhibitor, IκBα. Methods and Results — The adenovirus carrying human IκBα was applied immediately after balloon dilatation by a double-balloon catheter in a rabbit iliac artery restenosis model. Immunohistochemistry of IκBα revealed that mainly smooth muscle cells of the media but also cells of the adventitia were transduced and expressed the transgene IκBα for ≥8 days. At this time point, intercellular adhesion molecule-1 (30%) and monocyte chemotactic protein-1 (50%) expression, as well as recruitment of macrophages into the wounded area (90%), were significantly reduced in IκBα-treated vessels. In addition, expression of inhibitor of apoptosis proteins was reduced and the percentage of apoptotic cells was increased compared with control-treated...
Blood, 2001
In a variety of cell types, the transcription factor nuclear factor κB (NF-κB) functions as a med... more In a variety of cell types, the transcription factor nuclear factor κB (NF-κB) functions as a mediator of stress and immune responses. In endothelial cells (ECs), it controls the expression of genes encoding, eg, cytokines, cell adhesion molecules, and procoagulatory proteins. This study investigates the effect of NF-κB suppression on several pathophysiologic functions of ECs, including inflammation, coagulation, and angiogenesis. A recombinant adenovirus was generated for expression of a dominant negative (dn) mutant of IκB kinase 2 (IKK2), a kinase that acts as an upstream activator of NF-κB. dnIKK2 inhibited NF-κB, resulting in strongly reduced nuclear translocation and DNA binding activity of the transcription factor and lack of expression of several proinflammatory markers, including E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and interleukin-8. Concomitantly, inhibition of leukocyte binding to dnIKK2-expressing ECs could be demonstrated in...
Cardiovascular Pathology, 2004
Blood, 2009
Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic r... more Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up-regulation and partially by mRNA stabilization of inhibitor of apoptosis proteins, most prominently the X-linked inhibitor of apoptosis protein (XIAP). The antiapoptotic activity of uPA was dependent on its protease activity, the presence of uPA receptor (uPAR) and low-density lipoprotein receptor-related protein (LRP), but independent of the phosphatidylinositol 3 (PI3) kinase pathway, whereas vascular endothelial growth factor (VEGF)–induced antiapoptosis was PI3 kinase dependent. uPA-induced cell survival involved phosphorylation of p21-activated kinase 1 (Pak1) and the IκB kinase α that leads to nuclear factor κB (NF-κB) p52 activation. Indeed, blocking NF-κB activation by using specific NF-κB inhibitors abo...
Blood
VEGF, the most important angiogenic growth factor, is known to induce cell-survival mainly via ph... more VEGF, the most important angiogenic growth factor, is known to induce cell-survival mainly via phosphorylation of the pro-apoptotic proteins BAD, PED/PEA-2 or pro-caspase-9 or inhibition of SAPKs (stress activated kinases). These mechanisms are all dependent on the PI3-kinase/Akt pathway. We could show recently that VEGF also induces pro-uPA activation via the PI3-kinase signaling pathway beside and independent of the transcriptional upregulation of uPA. Active uPA does not only contribute to angiogenesis via its proteolytic properties, but also effectuates itself pro-angiogenic signalling by the induction of endothelial cell migration, proliferation and differentiation. We were interested whether generation of uPA upon VEGF is inducing an additional effect on endothelial cell survival. First, we compared VEGF with urokinase in respect to cell survival in apoptosis assays and observed a pivotal anti-apoptotic effect of both stimuli, dose dependently and dependent on the type of matr...
Water Research, 2016
Detection of enzymatic activities has been proposed as a rapid surrogate for the culture-based mi... more Detection of enzymatic activities has been proposed as a rapid surrogate for the culture-based microbiological pollution monitoring of water resources. This paper presents the results of tests on four fully automated prototype instruments for the on-site monitoring of beta-D-glucuronidase (GLUC) activity. The tests were performed on sediment-laden stream water in the Hydrological Open Air Laboratory (HOAL) during the period of March 2014 to March 2015. The dominant source of faecal pollution in the stream was swine manure applied to the fields within the catchment. The experiments indicated that instrument pairs with the same construction design yielded highly consistent results (R 2 ¼ 0.96 and R 2 ¼ 0.94), whereas the results between different designs were less consistent (R 2 ¼ 0.71). Correlations between the GLUC activity measured on-site and culture-based Escherichia coli analyses over the entire study period yielded R 2 ¼ 0.52 and R 2 ¼ 0.47 for the two designs, respectively. The correlations tended to be higher at the event scale. The GLUC activity was less correlated with suspended sediment concentrations than with E. coli, which is interpreted in terms of indicator applicability and the time since manure application. The study shows that this rapid assay can yield consistent results over a long period of on-site operation in technically challenging habitats. Although the use of GLUC activity as a proxy for culture-based assays could not be proven for the observed habitat, the study results suggest that this biochemical indicator has high potential for implementation in early warning systems.
In a variety of cell types, the transcription factor nuclear factor kB (NF-kB) func- tions as a m... more In a variety of cell types, the transcription factor nuclear factor kB (NF-kB) func- tions as a mediator of stress and immune responses. In endothelial cells (ECs), it controls the expression of genes encod- ing, eg, cytokines, cell adhesion mol- ecules, and procoagulatory proteins. This study investigates the effect of NF-kB suppression on several pathophysiologic functions of ECs, including inflammation,
Contamination of surface waters by pathogenic bacteria is a global health issue. Escherichia coli... more Contamination of surface waters by pathogenic bacteria is a global health issue. Escherichia coli (E.c.) is a lead indicator for fecal contamination, which can stem from natural sources, agricultural operations or dwellers. According to the state-of-the-art, bacterial water quality monitoring relies on laboratory testing of samples collected from waters like rivers and lakes, which is associated with time delays of 24h and more, see e.g the standard DIN EN ISO 9308-3. It is known that E.c. can be detected and enumerated by a fluorescence spectroscopic method. E. c. possesses a specific and very active enzyme called beta-D-glucuronidase (GUS). The catalytic activity of GUS is cleavage of glucuronides. For the assays, glucuronic acid attached to the fluorescent compound β-Methylumbelliferone (4 MU) is used. This enzymatic substrate (4-Methylumbelliferyl-b-D-glucuronide or 4-MUG) is not fluorescent itself, but the product of enzymatic reaction (4-MU) has very strong fluorescence. Based...
Chemie Ingenieur Technik
http://www.gitverlag.com/media/issue/3648/blaetterkatalog\_cit1213.pdf
Thrombosis and haemostasis, 1999
IntroductionThe urokinase-urokinase receptor (u-PA-u-PAR) system seems to play a crucial role in ... more IntroductionThe urokinase-urokinase receptor (u-PA-u-PAR) system seems to play a crucial role in a number of biological processes, including local fibrinolysis, tumor invasion, angiogenesis, neointima and atherosclerotic plaque formation, inflammation, and matrix remodeling during wound healing and development.1-6 Binding of urokinase to its specific receptor provides cells with a localized proteolytic potential. It stimulates conversion of cell surface-bound plasminogen into active plasmin, which, in turn, is required for proteolytic degradation of basement membrane components, including fibronectin, collagen, laminin, and proteoglycan core proteins.7 Moreover, plasmin activates other matrix-degrading enzymes, such as matrix metalloproteinases.8 Overexpression of u-PA/u-PAR correlates with tumor invasion and metastasis formation,9-13 while reduction of cell-surface bound u-PA and inhibition of u-PAR expression leads to a significant decrease of invasive and metastatic activity.14 Specific antagonists that suppress binding of u-PA to u-PAR have been shown to inhibit cell-surface plasminogen activation, tumor growth, and angiogenesis both in vitro and in vivo models.15,16 Independently of its proteolytic activity, u-PA is implicated in many biological processes that seem to require u-PAR-mediated intracellular signal transduction, such as proliferation, chemotactic movement and adhesion, migration, and differentiation.17 Data obtained in the late 1980s indicated that u-PA not only provides cells with local proteolytic activity, but might also be capable of transducing signals to the cell.18-22 At that time, however, the u-PAR has just been isolated, cloned, and identified as a glycosylphosphatidylinositol (GPI)-linked protein and not a transmembrane protein. Signaling via the u-PAR was, therefore, regarded as being unlikely, and the effects of u-PA on cell proliferation18-22 were thought to be mediated by proteolytic activation of latent growth factors. The assumption of direct signaling via u-PAR was, in fact, considered controversial, until about 10 years later when a physical association between u-PAR and signaling proteins was found.23 From this report on, several proteins associated with u-PAR have been identified. Now, u-PAR seems to be part of a large “signalosome” associated and interacting with several proteins on both the outside and inside of the cell.
Journal of Biological Chemistry, 1997
The urokinase-type plasminogen activator (uPA) binds to cells via a specific receptor attached to... more The urokinase-type plasminogen activator (uPA) binds to cells via a specific receptor attached to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. Despite the lack of a transmembrane domain, the urokinase receptor (uPAR) is capable of transducing extracellular signals affecting growth, migration, and adhesion. Several Tyr kinases of the src family as well as 1, 2, and 3 integrins were found to be associated with the uPAR. We found that in the human kidney epithelial line TCL-598, also components of the JAK1/STAT1 signal transduction pathway including gp130, are associated with uPAR as revealed by coimmunoprecipitation and are co-localized in caveolae. Upon clustering of uPA⅐uPAR complex by a monoclonal antibody, JAK1 associates with uPAR, which in turn leads to STAT1 phosphorylation, dimerization, specific binding to DNA, and gene activation. To prove the dependence of STAT1 activation on the uPAR, TCL-598 cells were treated with sense and antisense uPAR oligonucleotides. In antisense-treated cells in which uPAR expression was reduced to less then one third, activation of STAT1 by the clustering antibody was abolished while STAT1 activation by interferon-␥ was unaffected. Therefore, in this cell line, uPA⅐uPAR also utilizes the JAK1/STAT1 pathway for signaling, and gp130 might be the transmembrane adapter for this signal transduction pathway.
Journal of Thrombosis and Haemostasis, 2006
Innerhalb von 30 Minuten lässt sich durch ein neues Verfahren die Belastung von Wasser mit E. col... more Innerhalb von 30 Minuten lässt sich durch ein neues Verfahren die Belastung
von Wasser mit E. coli, Koliformen oder die Gesamtkeimzahl messen
Fibrinolysis and Proteolysis, 1998
This review focuses on signal transduction via the urokinase receptor, a very controversial issue... more This review focuses on signal transduction via the urokinase receptor, a very controversial issue. It describes data on membrane and extracellular matrix proteins interacting with this receptor, phosphorylation events induced by activation of the receptor, and influence of receptor activation on gene regulation and biologic functions of various cells. Due to the use of many different cells and culture conditions by different authors, and their focus on specific events within signaling cascades, a conclusive pathway of signal transduction via the urokinase receptor is still lacking. Actually this receptor seems to modify different signaling pathways used by integrins or cytokines rather than activate a signaling pathway of its own.
The FASEB Journal, 2001
The aim of this study was to investigate whether 8-iso-PGF 2α , a nonenzymatic free radical-induc... more The aim of this study was to investigate whether 8-iso-PGF 2α , a nonenzymatic free radical-induced oxidation product of arachidonic acid, activates endothelial cells (EC) to bind monocytes, which is a key initiating event in atherogenesis. Since thromboxane induces leukocyte adhesion ...
Journal of Biological Chemistry, 2002
In this study we have investigated the role of a specific corepressor of EGR-1, NAB2, to down-reg... more In this study we have investigated the role of a specific corepressor of EGR-1, NAB2, to down-regulate vascular endothelial growth factor (VEGF)-induced gene expression in endothelial cells and to inhibit angiogenesis. Firstly, we show a reciprocal regulation of EGR-1 and NAB2 following VEGF treatment. During the initial phase EGR-1 is rapidly induced and NAB2 levels are down-regulated. This is followed by a reduction of EGR-1 and a concomitant increase of NAB2. Secondly, using the tissue factor gene as a readout for VEGFinduced and EGR-1-regulated gene expression we demonstrate that NAB2 can completely block VEGF-induced tissue factor reporter gene activity. Thirdly, by adenovirus-mediated expression we show that NAB2 inhibits up-regulation of tissue factor, VEGF receptor-1, and urokinase plasminogen activator mRNAs even when a combination of VEGF and bFGF is used for induction. In addition, NAB2 overexpression significantly reduced tubule and sprout formation in two different in vitro angiogenesis assays and largely prevented the invasion of cells and formation of vessel-like structures in the murine Matrigel model. These data suggest that NAB2 regulation represents a mechanism to guarantee transient EGR-1 activity following exposure of endothelial cells to VEGF and that NAB2 overexpression could be used to inhibit signals involved in the early phase of angiogenesis.
Circulation, 2002
Background — To investigate the contribution of inflammation to postangioplasty lumen loss, we us... more Background — To investigate the contribution of inflammation to postangioplasty lumen loss, we used an adenoviral gene therapy approach to inhibit the central inflammatory mediator nuclear factor-κB (NF-κB) by overexpression of its natural inhibitor, IκBα. Methods and Results — The adenovirus carrying human IκBα was applied immediately after balloon dilatation by a double-balloon catheter in a rabbit iliac artery restenosis model. Immunohistochemistry of IκBα revealed that mainly smooth muscle cells of the media but also cells of the adventitia were transduced and expressed the transgene IκBα for ≥8 days. At this time point, intercellular adhesion molecule-1 (30%) and monocyte chemotactic protein-1 (50%) expression, as well as recruitment of macrophages into the wounded area (90%), were significantly reduced in IκBα-treated vessels. In addition, expression of inhibitor of apoptosis proteins was reduced and the percentage of apoptotic cells was increased compared with control-treated...
Blood, 2001
In a variety of cell types, the transcription factor nuclear factor κB (NF-κB) functions as a med... more In a variety of cell types, the transcription factor nuclear factor κB (NF-κB) functions as a mediator of stress and immune responses. In endothelial cells (ECs), it controls the expression of genes encoding, eg, cytokines, cell adhesion molecules, and procoagulatory proteins. This study investigates the effect of NF-κB suppression on several pathophysiologic functions of ECs, including inflammation, coagulation, and angiogenesis. A recombinant adenovirus was generated for expression of a dominant negative (dn) mutant of IκB kinase 2 (IKK2), a kinase that acts as an upstream activator of NF-κB. dnIKK2 inhibited NF-κB, resulting in strongly reduced nuclear translocation and DNA binding activity of the transcription factor and lack of expression of several proinflammatory markers, including E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and interleukin-8. Concomitantly, inhibition of leukocyte binding to dnIKK2-expressing ECs could be demonstrated in...
Cardiovascular Pathology, 2004
Blood, 2009
Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic r... more Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up-regulation and partially by mRNA stabilization of inhibitor of apoptosis proteins, most prominently the X-linked inhibitor of apoptosis protein (XIAP). The antiapoptotic activity of uPA was dependent on its protease activity, the presence of uPA receptor (uPAR) and low-density lipoprotein receptor-related protein (LRP), but independent of the phosphatidylinositol 3 (PI3) kinase pathway, whereas vascular endothelial growth factor (VEGF)–induced antiapoptosis was PI3 kinase dependent. uPA-induced cell survival involved phosphorylation of p21-activated kinase 1 (Pak1) and the IκB kinase α that leads to nuclear factor κB (NF-κB) p52 activation. Indeed, blocking NF-κB activation by using specific NF-κB inhibitors abo...
Blood
VEGF, the most important angiogenic growth factor, is known to induce cell-survival mainly via ph... more VEGF, the most important angiogenic growth factor, is known to induce cell-survival mainly via phosphorylation of the pro-apoptotic proteins BAD, PED/PEA-2 or pro-caspase-9 or inhibition of SAPKs (stress activated kinases). These mechanisms are all dependent on the PI3-kinase/Akt pathway. We could show recently that VEGF also induces pro-uPA activation via the PI3-kinase signaling pathway beside and independent of the transcriptional upregulation of uPA. Active uPA does not only contribute to angiogenesis via its proteolytic properties, but also effectuates itself pro-angiogenic signalling by the induction of endothelial cell migration, proliferation and differentiation. We were interested whether generation of uPA upon VEGF is inducing an additional effect on endothelial cell survival. First, we compared VEGF with urokinase in respect to cell survival in apoptosis assays and observed a pivotal anti-apoptotic effect of both stimuli, dose dependently and dependent on the type of matr...
Water Research, 2016
Detection of enzymatic activities has been proposed as a rapid surrogate for the culture-based mi... more Detection of enzymatic activities has been proposed as a rapid surrogate for the culture-based microbiological pollution monitoring of water resources. This paper presents the results of tests on four fully automated prototype instruments for the on-site monitoring of beta-D-glucuronidase (GLUC) activity. The tests were performed on sediment-laden stream water in the Hydrological Open Air Laboratory (HOAL) during the period of March 2014 to March 2015. The dominant source of faecal pollution in the stream was swine manure applied to the fields within the catchment. The experiments indicated that instrument pairs with the same construction design yielded highly consistent results (R 2 ¼ 0.96 and R 2 ¼ 0.94), whereas the results between different designs were less consistent (R 2 ¼ 0.71). Correlations between the GLUC activity measured on-site and culture-based Escherichia coli analyses over the entire study period yielded R 2 ¼ 0.52 and R 2 ¼ 0.47 for the two designs, respectively. The correlations tended to be higher at the event scale. The GLUC activity was less correlated with suspended sediment concentrations than with E. coli, which is interpreted in terms of indicator applicability and the time since manure application. The study shows that this rapid assay can yield consistent results over a long period of on-site operation in technically challenging habitats. Although the use of GLUC activity as a proxy for culture-based assays could not be proven for the observed habitat, the study results suggest that this biochemical indicator has high potential for implementation in early warning systems.
In a variety of cell types, the transcription factor nuclear factor kB (NF-kB) func- tions as a m... more In a variety of cell types, the transcription factor nuclear factor kB (NF-kB) func- tions as a mediator of stress and immune responses. In endothelial cells (ECs), it controls the expression of genes encod- ing, eg, cytokines, cell adhesion mol- ecules, and procoagulatory proteins. This study investigates the effect of NF-kB suppression on several pathophysiologic functions of ECs, including inflammation,
Contamination of surface waters by pathogenic bacteria is a global health issue. Escherichia coli... more Contamination of surface waters by pathogenic bacteria is a global health issue. Escherichia coli (E.c.) is a lead indicator for fecal contamination, which can stem from natural sources, agricultural operations or dwellers. According to the state-of-the-art, bacterial water quality monitoring relies on laboratory testing of samples collected from waters like rivers and lakes, which is associated with time delays of 24h and more, see e.g the standard DIN EN ISO 9308-3. It is known that E.c. can be detected and enumerated by a fluorescence spectroscopic method. E. c. possesses a specific and very active enzyme called beta-D-glucuronidase (GUS). The catalytic activity of GUS is cleavage of glucuronides. For the assays, glucuronic acid attached to the fluorescent compound β-Methylumbelliferone (4 MU) is used. This enzymatic substrate (4-Methylumbelliferyl-b-D-glucuronide or 4-MUG) is not fluorescent itself, but the product of enzymatic reaction (4-MU) has very strong fluorescence. Based...
Chemie Ingenieur Technik
http://www.gitverlag.com/media/issue/3648/blaetterkatalog\_cit1213.pdf
Thrombosis and haemostasis, 1999
IntroductionThe urokinase-urokinase receptor (u-PA-u-PAR) system seems to play a crucial role in ... more IntroductionThe urokinase-urokinase receptor (u-PA-u-PAR) system seems to play a crucial role in a number of biological processes, including local fibrinolysis, tumor invasion, angiogenesis, neointima and atherosclerotic plaque formation, inflammation, and matrix remodeling during wound healing and development.1-6 Binding of urokinase to its specific receptor provides cells with a localized proteolytic potential. It stimulates conversion of cell surface-bound plasminogen into active plasmin, which, in turn, is required for proteolytic degradation of basement membrane components, including fibronectin, collagen, laminin, and proteoglycan core proteins.7 Moreover, plasmin activates other matrix-degrading enzymes, such as matrix metalloproteinases.8 Overexpression of u-PA/u-PAR correlates with tumor invasion and metastasis formation,9-13 while reduction of cell-surface bound u-PA and inhibition of u-PAR expression leads to a significant decrease of invasive and metastatic activity.14 Specific antagonists that suppress binding of u-PA to u-PAR have been shown to inhibit cell-surface plasminogen activation, tumor growth, and angiogenesis both in vitro and in vivo models.15,16 Independently of its proteolytic activity, u-PA is implicated in many biological processes that seem to require u-PAR-mediated intracellular signal transduction, such as proliferation, chemotactic movement and adhesion, migration, and differentiation.17 Data obtained in the late 1980s indicated that u-PA not only provides cells with local proteolytic activity, but might also be capable of transducing signals to the cell.18-22 At that time, however, the u-PAR has just been isolated, cloned, and identified as a glycosylphosphatidylinositol (GPI)-linked protein and not a transmembrane protein. Signaling via the u-PAR was, therefore, regarded as being unlikely, and the effects of u-PA on cell proliferation18-22 were thought to be mediated by proteolytic activation of latent growth factors. The assumption of direct signaling via u-PAR was, in fact, considered controversial, until about 10 years later when a physical association between u-PAR and signaling proteins was found.23 From this report on, several proteins associated with u-PAR have been identified. Now, u-PAR seems to be part of a large “signalosome” associated and interacting with several proteins on both the outside and inside of the cell.
Journal of Biological Chemistry, 1997
The urokinase-type plasminogen activator (uPA) binds to cells via a specific receptor attached to... more The urokinase-type plasminogen activator (uPA) binds to cells via a specific receptor attached to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. Despite the lack of a transmembrane domain, the urokinase receptor (uPAR) is capable of transducing extracellular signals affecting growth, migration, and adhesion. Several Tyr kinases of the src family as well as 1, 2, and 3 integrins were found to be associated with the uPAR. We found that in the human kidney epithelial line TCL-598, also components of the JAK1/STAT1 signal transduction pathway including gp130, are associated with uPAR as revealed by coimmunoprecipitation and are co-localized in caveolae. Upon clustering of uPA⅐uPAR complex by a monoclonal antibody, JAK1 associates with uPAR, which in turn leads to STAT1 phosphorylation, dimerization, specific binding to DNA, and gene activation. To prove the dependence of STAT1 activation on the uPAR, TCL-598 cells were treated with sense and antisense uPAR oligonucleotides. In antisense-treated cells in which uPAR expression was reduced to less then one third, activation of STAT1 by the clustering antibody was abolished while STAT1 activation by interferon-␥ was unaffected. Therefore, in this cell line, uPA⅐uPAR also utilizes the JAK1/STAT1 pathway for signaling, and gp130 might be the transmembrane adapter for this signal transduction pathway.
Journal of Thrombosis and Haemostasis, 2006
Innerhalb von 30 Minuten lässt sich durch ein neues Verfahren die Belastung von Wasser mit E. col... more Innerhalb von 30 Minuten lässt sich durch ein neues Verfahren die Belastung
von Wasser mit E. coli, Koliformen oder die Gesamtkeimzahl messen