PMID: 11918547Mar 29, 2002Paper

Regulation of plasminogen activator inhibitor-1 secretion by urokinase and tissue plasminogen activator in rat epithelioid-type smooth muscle cells

British Journal of Haematology
Herbert K F Lau, Joanne Ho

Abstract

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 m...Continue Reading

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Citations

May 13, 2008·The Journal of Biological Chemistry·Sreerama ShettyRashmi S Shetty
Feb 7, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Paul D DiMustoGilbert R Upchurch
Dec 6, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yashodhar P BhandarySreerama Shetty
Nov 26, 2008·American Journal of Respiratory and Critical Care Medicine·Yashodhar P BhandarySreerama Shetty
Nov 24, 2011·Mutation Research·Hanna PiotrowskaMarek Murias
Jul 31, 2002·Biochemical and Biophysical Research Communications·Seiichi IshidaJun ichi Sawada
May 15, 2013·The American Journal of Pathology·Yashodhar P BhandarySreerama Shetty

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