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Growth factor-like action of phosphatidic acid


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+]i in 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 cytoplasmic pH, induces expression of the c-fos and c-myc proto-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.

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Moolenaar, W., Kruijer, W., Tilly, B. et al. Growth factor-like action of phosphatidic acid. Nature 323, 171–173 (1986).

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