Interleukin 2 does not induce phosphatidylinositol hydrolysis in activated T cells.
Hydrolysis of phosphatidylinositol-4,5-bisphosphate to diacylglycerol and myoinositol-1,4,5-trisphosphate is thought to be a primary event in the activation of cells by some growth factors, mitogenic lectins, and oncogenes. The mechanism whereby interleukin 2 (IL 2) binding to its receptor on activated T lymphocytes leads to cell proliferation has not been determined. Because the mitogenic has not been determined. Because the mitogenic action of IL 2 resembles that of some growth factors, the possible role of phosphatidylinositol breakdown in the activation of T cells by IL 2 was examined. In human or murine IL 2-sensitive cells, incubation with IL 2 did not alter the rate of turnover of phosphatidylinositol, phosphatidylinositol-5-phosphate, phosphatidylinositol-4,5-bisphosphate, or phosphatidylcholine in 32PO4-loaded cells. IL 2 also did not alter either the isotopic labeling of diacylglycerol or [3H]arachidonic acid release from cells. In addition, IL 2 did not alter the rate of formation of the phosphatidylinositol breakdown products myoinositol-1,4,5-trisphosphate, myoinositol-1,4-bisphosphate, or myoinositol-1-phosphate. In contrast, under similar conditions, IL 2 induced significant increases in [3H]thymidine incorporation and cell proliferation. Mitogenic lectins such as concanavalin A and phytohemagglutinin gave significant changes in isotopic labeling of phosphoinositols, diacylglycerols, and phosphatidylinositols, indicating that phosphatidylinositol hydrolysis induced by mitogenic lectins was detectable in the assay systems. IL 2, in contrast to other growth factors, does not appear to signal cells by increasing phosphatidylinositol breakdown.
Mills
G B
GB
Stewart
D J
DJ
Mellors
A
A
Gelfand
E W
EW
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D004075:Diglycerides / Q000096:biosynthesis; D006801:Humans; D006868:Hydrolysis; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D008563:Membrane Lipids / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D001095:Arachidonic Acids; D004075:Diglycerides; D007376:Interleukin-2; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D016718:Arachidonic Acid