Role of phospholipase D in the cAMP signal transduction pathway activated during fibroblast contraction of collagen matrices.

作者：Y G He, Frederick Grinnell · 发表于：The Journal of Cell Biology · 年份：1995 · DOI：10.1083/jcb.130.5.1197 · 被引用次数：15 · 研究领域：Protein Kinase Regulation and GTPase Signaling、Wnt/β-catenin signaling in development and cancer、Cellular Mechanics and Interactions

Fibroblast contraction of stressed collagen matrices results in activation of a cAMP signal transduction pathway. This pathway involves influx of extracellular Ca2+ ions and increased production of arachidonic acid. We report that within 5 min after initiating contraction, a burst of phosphatidic acid release was detected. Phospholipase D was implicated in production of phosphatidic acid based on observation of a transphosphatidylation reaction in the presence of ethanol that resulted in formation of phosphatidylethanol at the expense of phosphatidic acid. Activation of phospholipase D required extracellular Ca2+ ions and was regulated by protein kinase C. Ethanol treatment of cells also inhibited by 60-70% contraction-dependent release of arachidonic acid and cAMP but had no effect on increased cAMP synthesis after addition of exogenous arachidonic acid or on phospholipase A2 activity measured in cell extracts. Moreover, other treatments that inhibited the burst of phosphatidic acid release after contraction--chelating extracellular Ca2+ or down-regulating protein kinase C--also blocked contraction activated cyclic AMP signaling. These results were consistent with the idea that phosphatidic acid production occurred upstream of arachidonic acid in the contraction-activated cAMP signaling pathway.