Epithelial cell motility is triggered by activation of the EGF receptor through phosphatidic acid signaling
Epithelial cell motility is triggered by activation of the EGF receptor through phosphatidic acid signaling
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DOI：
10.1242/jcs.02858
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发表时间：
2006-04-15
影响因子：
4
通讯作者：
Klarlund, JK
中科院分区：
文献类型：
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作者：
Mazie, AR;Spix, JK;Klarlund, JK
磷脂酶D催化磷脂酰胆碱的水解产生磷脂酸，目前人们对阐明该分子的信使功能非常感兴趣。我们在这里报告说，角膜上皮和Madin达比犬肾细胞的伤口片诱导磷脂酶D的强烈激活，我们提供的证据表明，激活放大通过正反馈回路。磷脂酸的短链类似物在角膜和其他上皮细胞类型中强烈诱导运动。这些类似物的作用不是其转化为相应的二酰基甘油或溶血磷脂酸的结果，这意味着磷脂酸直接作用于一个或多个细胞靶点。引人注目的是，磷脂酸信号被发现刺激表皮生长因子受体（EGFR）通过反式激活过程。角膜上皮细胞片中伤口的愈合完全依赖于表皮生长因子受体信号传导，目前的数据表明，其激活是伤口诱导的磷脂酶D激活的结果。
Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid, and there is currently much interest in elucidating messenger functions for this molecule. We report here that wounding sheets of corneal epithelial and Madin Darby canine kidney cells induces strong activation of phospholipase D, and we provide evidence that activation is amplified through a positive feed-back loop. Short-chain analogues of phosphatidic acid induce motility robustly in corneal and other epithelial cell types. The effects of these analogues were not the result of their conversion to the corresponding diacylglycerol or lysophosphatidic acid, implying that phosphatidic acid acts directly on one or more cellular targets. Strikingly, phosphatidic acid signaling was found to stimulate the epidermal growth factor receptor ( EGFR) through a transactivation process. Healing of wounds in sheets of corneal epithelial cells is absolutely dependent on epidermal growth factor receptor signaling, and the present data suggest that its activation is a result of wound-induced phospholipase D activation.