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• W2155471992 startingPage "L591" @default.
• W2155471992 abstract "Mucus hyperproduction in pulmonary obstructive diseases results from increased goblet cell numbers and possibly increased cellular mucin synthesis, occurring in response to inflammatory mediators acting via receptor tyrosine kinases (RYK) and tyrosine phosphorylation (Y-Pi) signaling pathways. Yet, increased mucin synthesis does not lead necessarily to increased secretion, as mucins are stored in secretory granules and secreted in response to extracellular signals, commonly assumed to be mediated by G protein-coupled receptors (GPCRs). We asked whether activation 1) of Y-Pi signaling pathways, in principal, and 2) of the novel PKC isoform, nPKCδ, by Y-Pi, specifically, might lead to regulated mucin secretion. nPKCδ in SPOC1 cells was tyrosine phosphorylated by exposure to purinergic agonist (ATPγS) or PMA, actions that were blocked by the Src kinase inhibitor, PP1. Mucin secretion, however, was not affected by PP1. Hence, activation of nPKCδ by Y-Pi is unlikely to participate in GPCR-related mucin secretion. Mucin secretion from both SPOC1 and normal human bronchial epithelial (NHBE) cells was stimulated by generalized protein Y-Pi induced by the tyrosine phosphatase inhibitor, pervanadate (PV). PV-induced SPOC1 cell mucin secretion was not affected by inhibition of Src kinases (genistein or PP1), or of PI3 kinase (LY-294002). MAP kinase pathway inhibitors, RAF1 kinase inhibitor-I and U0126 (MEK), inhibited SPOC1 cell PV-induced secretion by ∼50%. Significantly, the phospholipase C (PLC) inhibitor, U-73122, essentially abolished PV- and ATPγS-induced mucin secretion from both SPOC1 and NHBE cells. Hence, PLC signaling may play a key role in regulated mucin secretion, whether the event is initiated by mediators interacting with GPCRs or RYKs." @default.
• W2155471992 created "2016-06-24" @default.
• W2155471992 creator A5005672335 @default.
• W2155471992 creator A5078790179 @default.
• W2155471992 date "2007-09-01" @default.
• W2155471992 modified "2023-09-23" @default.
• W2155471992 title "Regulation of airway goblet cell mucin secretion by tyrosine phosphorylation signaling pathways" @default.
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• W2155471992 doi "https://doi.org/10.1152/ajplung.00150.2007" @default.
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