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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2002-3-28
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pubmed:abstractText |
Tissue plasminogen activator (tPA) and urokinase (uPA) are targets of plasminogen activator inhibitor-1 (PAI-1) inhibition. We have previously shown that both proteases can also induce PAI-1 secretion in rat smooth muscle cells (SMCs). We now report that both proteases appear to use very similar cellular mechanisms for signal transduction. They induced PAI-1 secretion using a pathway(s) involving protein kinase C (PKC). They also activated the Raf/Mek/mitogen-activated protein kinase (MAPK) pathway, which lies downstream of PKC activation. Activation of protein kinase A (PKA), however, lowered PAI-1 secretion induced by uPA and tPA, as a result of an inhibition of the PKC pathway and inhibition of Raf, Mek and MAPK phosphorylations. Src and syk family non-receptor tyrosine kinases (TK) were also involved in PAI-1 induction. The mechanisms of interaction of these tyrosine kinases with other pathways appeared to be quite different: src appeared to act within the PKC and PKA pathways, while syk operated independently of these pathways. Furthermore, whereas src inhibition resulted in inhibition of Raf/Mek/Erk phosphorylations, syk inhibition could only inhibit Mek and Erk phosphorylations but not the phosphorylation of Raf. These multiple pathways utilized by uPA and tPA to modulate PAI-1 secretion might be involved in determining the proteolytic or antiproteolytic potential of the SMCs under different pathophysiological conditions.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/3,3',4,5'-tetrahydroxystilbene,
http://linkedlifedata.com/resource/pubmed/chemical/8-Bromo Cyclic Adenosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine,
http://linkedlifedata.com/resource/pubmed/chemical/Carbazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Genistein,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/KT 5720,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-...,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/Stilbenes,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0007-1048
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
151-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11918547-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:11918547-8-Bromo Cyclic Adenosine Monophosphate,
pubmed-meshheading:11918547-Animals,
pubmed-meshheading:11918547-Bucladesine,
pubmed-meshheading:11918547-Carbazoles,
pubmed-meshheading:11918547-Cells, Cultured,
pubmed-meshheading:11918547-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:11918547-Enzyme Inhibitors,
pubmed-meshheading:11918547-Flavonoids,
pubmed-meshheading:11918547-Genistein,
pubmed-meshheading:11918547-Indoles,
pubmed-meshheading:11918547-Isoquinolines,
pubmed-meshheading:11918547-MAP Kinase Signaling System,
pubmed-meshheading:11918547-Muscle, Smooth, Vascular,
pubmed-meshheading:11918547-Phosphodiesterase Inhibitors,
pubmed-meshheading:11918547-Phosphorylation,
pubmed-meshheading:11918547-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:11918547-Protein Kinase C,
pubmed-meshheading:11918547-Protein-Tyrosine Kinases,
pubmed-meshheading:11918547-Pyrroles,
pubmed-meshheading:11918547-Rats,
pubmed-meshheading:11918547-Signal Transduction,
pubmed-meshheading:11918547-Stilbenes,
pubmed-meshheading:11918547-Sulfonamides,
pubmed-meshheading:11918547-Tissue Plasminogen Activator,
pubmed-meshheading:11918547-Urokinase-Type Plasminogen Activator,
pubmed-meshheading:11918547-src-Family Kinases
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pubmed:year |
2002
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pubmed:articleTitle |
Regulation of plasminogen activator inhibitor-1 secretion by urokinase and tissue plasminogen activator in rat epithelioid-type smooth muscle cells.
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pubmed:affiliation |
Division of Hematology, Department of Medicine, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. lauh@smh.toronto.on.ca
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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