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Microbiology 146 (2000), 377-384
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Microbiology (2000), 146, 377-384.
© 2000 Society for General Microbiology


Physiology and Growth

Long-chain alkyl ester of AMP acts as an antagonist of glucose-induced signal transduction that mediates activation of plasma membrane proton pump in Saccharomyces cerevisiae

Toshio Tanaka1, Keiji Nakayama1, Kiyotaka Machida1 and Makoto Taniguchi1

Department of Bio- and Geoscience, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan1

Author for correspondence: Toshio Tanaka. Tel: +81 6 6605 3163. Fax: +81 6 6605 3164. e-mail: tanakato{at}sci.osaka-cu.ac.jp

One of the long-chain alkyl esters of AMP, adenosine 5'-hexadecylphosphate (AMPC16), exhibited a cytotoxic growth inhibitory effect on cells of various yeast strains. The growth inhibitory effect of AMPC16 on Saccharomyces cerevisiae cells was observed only in medium containing Mg2+, which accelerated cellular uptake of the nucleotide analogue. In the presence of Mg2+, AMPC16 completely inhibited glucose-induced extracellular acidification by the intact cells and also interfered with activation of the plasma membrane ATPase, but did not directly inhibit the ATPase activity itself. AMPC16 treatment prevented cells from increasing their intracellular sn-1,2-diacylglycerol (DAG) level in response to glucose, whereas the inhibition of proton extrusion by the cells could be largely reversed by the coaddition of a membrane-permeable DAG analogue. The DAG analogue, a physiological activator of protein kinase C (PKC), was not protective against the inhibition of glucose-induced proton extrusion by staurosporine, which is capable of directly interfering with the action of PKC. These results implied that AMPC16 caused a Mg2+-dependent cytotoxic effect on Sac. cerevisiae cells by interfering with a phosphatidylinositol type of signal that mediates activation of the plasma membrane proton pump.

Keywords: Saccharomyces cerevisiae, plasma membrane H+-ATPase, signal transduction, nucleotide analogue

Abbreviations: AMPC12, adenosine 5'-dodecylphosphate; AMPC16, adenosine 5'-hexadecylphosphate; AMPC20, adenosine 5'-eicosylphosphate; DAG, diacylglycerol; DES, diethylstilboestrol; PKC, protein kinase C; UMPC12, uridine 5'-dodecylphosphate; UMPC16, uridine 5'-hexadecylphosphate; UMPC20, uridine 5'-eicosylphosphate




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