Wortmannin has opposite effects on phorbol ester-induced DNA synthesis and phosphatidylcholine hydrolysis. 1995

Z Kiss, and M Tomono
Hormel Institute, University of Minnesota, Austin 55912, USA.

The tumor promoter phorbol 12-myristate 13-acetate (PMA) and hormonal activators of protein kinase C (PKC) commonly stimulate phospholipase D (PLD)-mediated formation of phosphatidic acid from phosphatidylcholine (PtdCho) in fibroblasts and other cell types. On the basis that phosphatidic acid is a mitogen, PLD is often considered to have a major role in the regulation of cell growth by PKC activators. However, we found that in NIH 3T3 fibroblasts wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), strongly inhibited DNA synthesis induced by 100 nM PMA, while it actually enhanced PMA-stimulated PtdCho hydrolysis. These results indicate that stimulation of PLD activity is either not required or not sufficient for the mitogenic action of PMA.

UI MeSH Term Description Entries
D010169 Palmitic Acids A group of 16-carbon fatty acids that contain no double bonds. Acids, Palmitic
D010712 Phosphatidic Acids Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups. Ammonium Phosphatidate,Diacylglycerophosphates,Phosphatidic Acid,Acid, Phosphatidic,Acids, Phosphatidic,Phosphatidate, Ammonium
D010713 Phosphatidylcholines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety. Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D010739 Phospholipase D An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4. Lecithinase D,Phosphatidylcholine Phosphohydrolase
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D000077191 Wortmannin An androstadiene metabolite produced by the fungi PENICILLIUM funiculosum that inhibits PHOSPHATIDYLINOSITOL-3-KINASES and alloantigen-specific activation of T-LYMPHOCYTES in human tumor cell lines. It is widely used in CELL BIOLOGY research and has broad therapeutic potential. MS 54,MS-54,MS54
D000730 Androstadienes Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013755 Tetradecanoylphorbol Acetate A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA. Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer

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