Showing papers by "Denise R. Cooper published in 1987"
TL;DR: Both phospholipid effects of insulin seem important for generating diacylglycerol and other phospholipsid-derived intracellular signaling substances.
Abstract: The mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes were examined. When [3H]arachidonate labeling of phospholipids was used as an indicator of phospholipase C activation, transient increases in [3H]diacylglycerol were observed between 0.5 and 10 minutes after the onset of insulin treatment. With [3H]glycerol labeling as an indicator of de novo phospholipid synthesis, [3H]diacylglycerol was increased maximally at 1 minute and remained elevated for 20 minutes. [3H]Glycerol-labeled diacylglycerol was largely derived directly from phosphatidic acid. Insulin increased de novo phosphatidic acid synthesis within 5 to 10 seconds; within 1 minute, this synthesis was 60 times greater than that of controls. Thus, the initial increase in diacylglycerol is due to both increased hydrolysis of phospholipids and a burst of de novo phosphatidic acid synthesis. After 5 to 10 minutes, de novo phosphatidic acid synthesis continues as a major source of diacylglycerol. Both phospholipid effects of insulin seem important for generating diacylglycerol and other phospholipid-derived intracellular signaling substances.
187 citations
TL;DR: Early insulin-induced increases in membrane and cytosolic protein kinase C activity may be related to increased diacylglycerol generation from de novo phosphatidic acid synthesis, as there were rapid increases in [3H] Glycerol incorporation into diacyLglycerols at later, as well as very early time points.
160 citations
TL;DR: Chronic TPA‐induced ‘desensitization’ or ‘depletion’ of cellular protein kinase C is more apparent than real, and is not a valid means for evaluating the role of C‐kinase in hormone action.
26 citations
TL;DR: It appears that the de novo phospholipid synthesis effect of ACTH is accompanied by increases in diacylglycerol and translocative activation of the C-kinase system.
19 citations
Journal Article•
1 citations
01 Jan 1987
TL;DR: There are two major mechanisms whereby hormones and other agonists alter phospholipid metabolism and generate intracellular signaling substances in their respective target tissues, viz.,ospholipase activation and phospholIPid synthesis.
Abstract: There are two major mechanisms whereby hormones and other agonists alter phospholipid metabolism and generate intracellular signaling substances in their respective target tissues, viz., phospholipase activation and phospholipid synthesis. The most widely popularized mechanism involves the activation of a specific phospholipase C which hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2).1 This hydrolysis generates inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which, respectively, mobilize Ca++ from intracellular stores and activate protein kinase C2 and other possibly related kinases. This hydrolytic mechanism is probably operative in the action of most agonists which operate via cell surface receptors and use Ca++ as a major intracellular signaling substance. In addition to PIP2 hydrolysis, other types of phospholipase C may be activated, causing the hydrolysis of phosphatidylcholine (PC),3 phosphatidylinositol (PI) or a PI-glucosamine complex (PI-glycan).4 While it is clear that cell surface receptors are coupled to the PIP2 phospholipase C through GTP-binding proteins (which may or may not be inhibited by pertussis toxin), little is known about the mechanisms whereby receptors activate other forms of phospholipase C.
1 citations