Br J Haematol 2002,
PMID: 11918547
Lau, Herbert K F; Ho, Joanne
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.
Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
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Text Mining Data
plasminogen — tissue plasminogen activator: "
Regulation of
plasminogen activator inhibitor-1 secretion by urokinase and
tissue plasminogen activator in rat epithelioid-type smooth muscle cells
"
PAI-1 → tPA: "
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
"
PAI-1 → uPA: "
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
"
protein kinase A (PKA) → MAPK: "
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
"
PAI-1 → Src: "
Src and syk family non-receptor tyrosine kinases ( TK ) were also involved in PAI-1 induction
"
Manually curated Databases
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