Regulation and function of an insulin-sensitive glycosyl-phosphatidylinositol during T lymphocyte activation.
A combination of metabolic labeling and chemical or enzymatic modification was employed to isolate and biochemically characterize a set of glycosyl-phosphatidylinositol (gly-PI) molecules synthesized by T lymphocytes. Gly-PI displayed unique patterns of synthesis following mitogen activation relative to the phosphoinositides and major structural lipids. The increase with time in gly-PI was paralleled by the appearance of insulin receptors. Gly-PI molecules were sensitive to hydrolysis by a PI-specific phospholipase C and were rapidly (15 sec) degraded in response to insulin binding. The product of this hydrolysis is believed to be a novel inositol phosphate-glycan (IP-gly) that was shown to inhibit the activity of a cAMP-dependent protein kinase. These results demonstrate that T cells contain a structurally related set of gly-PI molecules, at least one of which is sensitive to insulin and may function as a second messenger of hormone action.
Gaulton
G N
GN
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Kelly
K L
KL
Pawlowski
J
J
Mato
J M
JM
Jarett
L
L
D000818:Animals; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D006031:Glycosylation; D006868:Hydrolysis; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D010716:Phosphatidylinositols / Q000032:analysis / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D011972:Receptor, Insulin / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D010716:Phosphatidylinositols; D011972:Receptor, Insulin