There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.

Inositol trisphosphate, a novel second messenger in cellular signal transduction.

CARDIOVASCULAR disease remains the chief cause of death in the United States and Western Europe, and atherosclerosis, the principal cause of myocardial and cerebral infarction, accounts for the majority of these deaths.1 This review, like its predecessor,2 will not attempt to cover all literature on atherosclerosis. In a previous review of the pathogenesis of atherosclerosis,2 Glomset and I discussed various hypotheses of atherogenesis2 3 4 5 6 7 and emphasized the importance of intimal smooth-muscle proliferation as the key event in the development of the advanced lesions of atherosclerosis. The response-to-injury hypothesis of atherogenesis2 3 4 5 6 proposes that "injury" to the endothelium is the initiating event in . . .

The Pathogenesis of Atherosclerosis — An Update

/pdf/inositol-trisphosphate-and-diacylglycerol-as-second-4drzjsg27y.pdf

Inositol trisphosphate and diacylglycerol as second messengers.

The primary structure of the receptor for platelet-derived growth factor (PDGF), determined by means of cloning a cDNA that encodes the murine pre-PDGF receptor, is closely related to that of the v-kit oncogene product and the receptor for macrophage colony stimulating factor (CSF-1). Common structural features include the presence of long sequences that interrupt the tyrosine-specific protein kinase domains of each molecule. The PDGF and CSF-1 receptors also share a characteristic distribution of extracellular cysteine residues. Ubiquitin is covalently bound to the purified PDGF receptor, the human gene for which is on chromosome 5.

Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors

There is evidence that the polymerization of actin takes place at the plasma membrane, and that profilactin (profilin/actin complex), the unpolymerized form of actin found in extracts of many non-muscle cells, serves as the immediate precursor. Both isolated profilin and profilactin interact with detergent when analysed by charge shift electrophoresis, indicating that they have amphipathic properties and may be able to interact directly with the plasma membrane. We demonstrate here that isolated profilin, as well as the profilactin complex, interacts with anionic phospholipids. Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) was found to be the most active phospholipid, causing a rapid and efficient dissociation of profilactin with a concomitant polymerization of the actin in appropriate conditions. These and other observations suggest the possibility of a relationship between the induction of actin filament formation and the increased activity in the phosphatidylinositol cycle seen as a result of ligand-receptor interactions in various systems.

Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin

Packing and electrostatic behavior of sn-2-docosahexaenoyl and -arachidonoyl phosphoglycerides.

Three series of experiments have been performed to study plasma lipoprotein metabolism in familial lecithin: cholesterol acyltransferase deficiency. In one series diets that contained little or no long chain triglyceride decreased the concentrations of several of the lipoproteins, particularly including the large unesterified cholesterol- and lecithin-rich lipoproteins in the class of d 1.019–1.063 g/ml. In the second series of experiments post-heparin lipolytic activity was found to increase the concentrations of the same low density lipoproteins in vivo. In the third series of experiments incubation with lecithin: cholesterol acyltransferase in vitro was found to decrease the unesterified cholesterol and lecithin of the large low density lipoproteins and to increase the cholesteryl ester of normal-sized very low, low, and high density lipoproteins. These findings are compatible with the concept that the large low density lipoproteins accumulate in the patients' plasma because chylomicron surface lipids ...

Plasma Lipoprotein Metabolism in Familial Lecithin: Cholesterol Acyltransferase Deficiency

Structural Determinants of the Packing and Electrostatic Behavior of Unsaturated Phosphoglycerides

http://www.jbc.org/content/256/23/12329.full.pdf

Early changes in phosphatidylinositol and arachidonic acid metabolism in quiescent swiss 3T3 cells stimulated to divide by platelet-derived growth factor.

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Packing and electrostatic behavior of sn-2-docosahexaenoyl and -arachidonoyl phosphoglycerides.

Plasma Lipoprotein Metabolism in Familial Lecithin: Cholesterol Acyltransferase Deficiency

Structural Determinants of the Packing and Electrostatic Behavior of Unsaturated Phosphoglycerides

Early changes in phosphatidylinositol and arachidonic acid metabolism in quiescent swiss 3T3 cells stimulated to divide by platelet-derived growth factor.