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首页> 外文期刊>American Journal of Physiology >Regulation of airway goblet cell mucin secretion by tyrosine phosphorylation signaling pathways.
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Regulation of airway goblet cell mucin secretion by tyrosine phosphorylation signaling pathways.

机译：酪氨酸磷酸化信号通路调节气道杯状细胞黏蛋白的分泌。

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摘要

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, nPKCdelta, by Y-Pi, specifically, might lead to regulated mucin secretion. nPKCdelta in SPOC1 cells was tyrosine phosphorylated by exposure to purinergic agonist (ATPgammaS) or PMA, actions that were blocked by the Src kinase inhibitor, PP1. Mucin secretion, however, was not affected by PP1. Hence, activation of nPKCdelta 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 approximately 50%. Significantly, the phospholipase C (PLC) inhibitor, U-73122, essentially abolished PV- and ATPgammaS-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.
机译：肺梗阻性疾病中的粘液过度产生是由于杯状细胞数量增加，可能是细胞粘蛋白合成增加所致，这是通过受体酪氨酸激酶（RYK）和酪氨酸磷酸化（Y-Pi）信号传导途径引起的炎症介质而引起的。然而，粘蛋白的合成不一定会导致分泌增加，因为粘蛋白被储存在分泌颗粒中，并响应于通常被认为是由G蛋白偶联受体（GPCR）介导的细胞外信号而分泌。我们询问是否由Y-Pi激活1）原理上的Y-Pi信号通路，以及2）新的PKC同种型nPKCdelta，具体而言是否可能导致粘蛋白分泌调节。 SPOC1细胞中的nPKCdelta通过暴露于嘌呤能激动剂（ATPgammaS）或PMA而被酪氨酸磷酸化，而Src激酶抑制剂PP1阻止了该作用。然而，粘蛋白的分泌不受PP1的影响。因此，Y-Pi激活nPKCdelta不太可能参与GPCR相关的粘蛋白分泌。酪氨酸磷酸酶抑制剂过钒酸盐（PV）诱导的泛化蛋白Y-Pi刺激SPOC1和正常人支气管上皮（NHBE）细胞分泌粘蛋白。 PV诱导的SPOC1细胞粘蛋白分泌不受Src激酶（染料木黄酮或PP1）或PI3激酶（LY-294002）抑制的影响。 MAP激酶途径抑制剂RAF1激酶抑制剂I和U0126（MEK）抑制SPOC1细胞PV诱导的分泌约50％。重要的是，磷脂酶C（PLC）抑制剂U-73122基本上消除了SPOC1和NHBE细胞中PV和ATPgammaS诱导的粘蛋白分泌。因此，无论事件是由与GPCR或RYK相互作用的介体引发的，PLC信号传导可能在粘蛋白分泌的调节中起关键作用。

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