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• W2100505526 abstract "We investigated proteinase-activated receptor-2 (PAR(2))-triggered signal transduction pathways causing increased prostaglandin E(2) (PGE(2)) formation in human lung-derived A549 epithelial cells. The PAR(2) agonist, SLIGRL-NH(2) (Ser-Leu-Ile-Gly-Arg-Leu-amide), evoked immediate cytosolic Ca(2+) mobilization and delayed (0.5-3 h) PGE(2) formation. The PAR(2)-triggered PGE(2) formation was attenuated by inhibition of the following signal pathway enzymes: cyclooxygenases 1 and 2 (COX-1 and COX-2, respectively), cytosolic Ca(2+)-dependent phospholipase A(2) (cPLA(2)), the mitogen-activated protein kinases (MAPKs), mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) and p38 MAPK, Src family tyrosine kinase, epidermal growth factor (EGF) receptor tyrosine kinase (EGFRK), and protein kinase C (PKC), but not by inhibition of matrix metalloproteinases. SLIGRL-NH(2) caused prompt (5 min) and transient ERK phosphorylation, blocked in part by inhibitors of PKC and tyrosine kinases but not by an EGFRK inhibitor. SLIGRL-NH(2) also evoked a relatively delayed (15 min) and persistent (30 min) phosphorylation of p38 MAPK, blocked by inhibitors of Src and EGFRK but not by inhibitors of COX-1 or COX-2. SLIGRL-NH(2) elicited a Src inhibitor-blocked prompt (5 min) and transient phosphorylation of the EGFRK. SLIGRL-NH(2) up-regulated COX-2 protein and/or mRNA levels that were blocked by inhibition of p38 MAPK, EGFRK, Src, and COX-2 but not MEK-ERK. SLIGRL-NH(2) also caused COX-1-dependent up-regulation of microsomal PGE synthase-1 (mPGES-1). We conclude that PAR(2)-triggered PGE(2) formation in A549 cells involves a coordinated up-regulation of COX-2 and mPGES-1 involving cPLA(2), increased cytosolic Ca(2+), PKC, Src, MEK-ERK, p38 MAPK, Src-mediated EGF receptor trans-activation, and also metabolic products of both COX-1 and COX-2." @default.
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• W2100505526 date "2005-08-24" @default.
• W2100505526 modified "2023-10-05" @default.
• W2100505526 title "Signal Transduction for Proteinase-Activated Receptor-2-Triggered Prostaglandin E₂ Formation in Human Lung Epithelial Cells" @default.
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• W2100505526 doi "https://doi.org/10.1124/jpet.105.089490" @default.
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