GROWTH FACTOR-LIKE ACTION OF PHOSPHATIDIC-ACID
GROWTH FACTOR-LIKE ACTION OF PHOSPHATIDIC-ACID
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DOI：
10.1038/323171a0
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发表时间：
1986-09-11
期刊：
影响因子：
64.8
通讯作者：
DELAAT, SW
中科院分区：
文献类型：
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作者：
MOOLENAAR, WH;KRUIJER, W;DELAAT, SW
磷脂酸 (PA) 是一种有趣的磷脂，在受体刺激的磷酸肌醇分解过程中快速产生，通常被认为在活化细胞中充当 Ca2+ 离子载体 11-5。 PA-离子载体假说得到以下事实的支持：外源应用的 PA 刺激各种细胞中的 Ca2+ 摄取4-6，并能引起 Ca2+ 介导的生理反应2-5，但尚不清楚 PA 积累是否影响细胞质游离 Ca2+ 浓度 ([Ca2+]i)。在这里，我们报道 PA 引起培养细胞中 [Ca2+]i 的短暂升高，不是通过刺激 Ca2+ 内流，而是通过从细胞内储存中释放 Ca2+ 来引起。我们进一步表明，PA 会引起生长因子样作用，因为它会提高细胞质 pH 值，诱导 c-fosandc-myc 原癌基因的表达并刺激 DNA 合成。我们的结果表明，与离子载体不同，PA 通过触发磷酸肌醇水解发挥作用，随后形成第二信使，如三磷酸肌醇，信号 Ca2+ 释放。此外，我们的数据强化了这样的观点：任何通过磷脂酶 C 发挥作用的 Cai2+ 动员刺激最终都可能充当生长因子。
Phosphatidic acid (PA), an intriguing phospholipid that is rapidly produced during receptor-stimulated breakdown of phosphoinosi-tides, has often been proposed to function as a Ca2+ionophore in activated cells11–5. The PA-ionophore hypothesis is supported by the fact that exogenously applied PA stimulates Ca2+uptake in various cells4–6 and can evoke Ca2+-mediated physiological responses2–5, but it is not known whether PA accumulation affects cytoplasmic free Ca2+concentration ([Ca2+]i). Here we report that PA elicits a transient rise in [Ca2+]iin cultured cells, not by stimulating Ca2+influx, but, surprisingly, by releasing Ca2+from intracellular stores. We further show that PA evokes growth factor-like effects in that it raises cytoplasmicpH, induces expression of thec-fosandc-mycproto-oncogenes and stimulates DNA synthesis. Our results indicate that, unlike an ionophore, PA acts by triggering the hydrolysis of phosphoinositides, with consequent formation of second messengers such as inositol trisphosphate signalling Ca2+release. Furthermore, our data strengthen the notion that any Cai2+-mobilizing stimulus acting through phospholipase C may ultimately function as a growth factor.