Transduction of mitogenic signals in T lymphocytes. Role of inositol phospholipids for the rapid activation of ornithine decarboxylase.
Treatment of human T lymphocytes with mitogenic ligands, such as concanavalin A (Con A), induces a rapid activation of the enzyme ornithine decarboxylase (ODC). This activation occurs within minutes and is completely inhibited when the cells are treated with 1 mM Li+ (in an inositol-free medium) prior to stimulation with Con A. In the presence of 1 mM myo-inositol Li+ has no effect on the Con A-induced activation of ODC. To elucidate why inositol is needed for the mitogen-induced activation of ODC in T lymphocytes, we tested the ability of different inositol metabolites to reverse the inhibitory effect of Li+. Here we report that inositol phospholipids, in addition to inositol, reverse the Li+-induced inhibition of ODC activation, while all other inositol derivatives tested were ineffective. This indicates that Li+ does not block the activation of ODC by inhibiting the generation of inositol phosphates, but rather by a mechanism which is circumvented if inositol phospholipids are added. The molecular mechanisms involved in the rapid activation of ODC by mitogens in human T lymphocytes apparently require inositol phospholipids, but are not directly mediated by inositol-1,4,5-trisphosphate (IP3) alone, diacylglycerol alone, or other inositol phosphates.
D004789:Enzyme Activation; D006801:Humans; D007294:Inositol / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D008213:Lymphocyte Activation; D009955:Ornithine Decarboxylase / Q000032:analysis*; D010716:Phosphatidylinositols / Q000494:pharmacology*; D011700:Putrescine / Q000032:analysis; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; C044259:inositol 1,4-bis(phosphate); D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate; D008094:Lithium; D009955:Ornithine Decarboxylase; D011700:Putrescine