Glycosylphosphatidylinositol: a candidate system for interleukin-2 signal transduction.
The mechanism of interleukin-2 (IL-2) signal transduction was analyzed by use of an inducible B lymphoma. Like normal antigen-activated B lymphocytes, the lymphoma cells respond to IL-2 by proliferating and differentiating into antibody-secreting cells; both responses are blocked by a second interleukin, IL-4. Analyses of the signaling pathway showed that IL-2 stimulated the rapid hydrolysis of an inositol-containing glycolipid to yield two possible second messengers, a myristylated diacylglycerol and an inositol phosphate-glycan. The myristylated diacylglycerol response exhibited the same IL-2 dose dependence as the growth and differentiative responses, and the generation of both hydrolysis products was inhibited by IL-4. These correlations implicate the glycosyl-phosphatidylinositol system in the intracellular relay of the IL-2 signal.
Eardley
D D
DD
Department of Biological Sciences, University of California, Santa Barbara 93106.
Koshland
M E
ME
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D004075:Diglycerides / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006017:Glycolipids / Q000502:physiology*; D017261:Glycosylphosphatidylinositols; D007294:Inositol / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000502:physiology*; D011134:Polysaccharides / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D004075:Diglycerides; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D007376:Interleukin-2; D009227:Myristic Acids; D010716:Phosphatidylinositols; D011134:Polysaccharides; D019814:Myristic Acid; D015847:Interleukin-4; D016718:Arachidonic Acid; D007294:Inositol; D005944:Glucosamine