Inositol phospholipids and cell surface receptor function.
About: This article is published in Biochimica et Biophysica Acta.The article was published on 1975-03-25. It has received 2273 citations till now. The article focuses on the topics: Cell surface receptor & Cell membrane.
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TL;DR: Protein kinase C probably serves as a receptor for the tumour promoters and further exploration of the roles of this enzyme may provide clues for understanding the mechanism of cell growth and differentiation.
Abstract: Protein kinase C has a crucial role in signal transduction for a variety of biologically active substances which activate cellular functions and proliferation. When cells are stimulated, protein kinase C is transiently activated by diacylglycerol which is produced in the membrane during the signal-induced turnover of inositol phospholipids. Tumour-promoting phorbol esters, when intercalated into the cell membrane, may substitute for diacylglycerol and permanently activate protein kinase C. The enzyme probably serves as a receptor for the tumour promoters. Further exploration of the roles of this enzyme may provide clues for understanding the mechanism of cell growth and differentiation.
6,917 citations
TL;DR: 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.
Abstract: 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.
5,712 citations
TL;DR: A novel role of this protein kinase system seems to give a logical basis for clarifying the biochemical mechanism of signal transduction, and to add a new dimension essential to the understanding of cell-to-cell communication.
Abstract: Protein kinase C, an enzyme that is activated by the receptor-mediated hydrolysis of inositol phospholipids, relays information in the form of a variety of extracellular signals across the membrane to regulate many Ca2+-dependent processes. At an early phase of cellular responses, the enzyme appears to have a dual effect, providing positive forward as well as negative feedback controls over various steps of its own and other signaling pathways, such as the receptors that are coupled to inositol phospholipid hydrolysis and those of some growth factors. In biological systems, a positive signal is frequently followed by immediate negative feedback regulation. Such a novel role of this protein kinase system seems to give a logical basis for clarifying the biochemical mechanism of signal transduction, and to add a new dimension essential to our understanding of cell-to-cell communication.
5,006 citations
TL;DR: Kinetic analysis indicates that TPA can substitute for diacylglycerol and greatly increases the affinity of the enzyme for Ca2+ as well as for phospholipid, and various phorbol derivatives which have been shown to be active in tumor promotion are also capable of activating this protein kinase in in vitro systems.
4,562 citations
3,341 citations
References
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Journal Article•
TL;DR: A diagrammatic summary of the membrane actions of anesthetics and tran-quilizers is shown, and the membrane fluidization may explain the enhanced neurosecretion of membrane-bound materials, by a mechanism of membranes-membrane fusion.
Abstract: A diagrammatic summary of the membrane actions of anesthetics and tran-quilizers is shown in figure 15. According to the definition of an anesthetic as a drug which directly blocks the membrane action potential, without appreciably affecting the resting potential, a wide variety of lipid-soluble compounds may be considered as anesthetics. Under conditions of general anesthesia the membrane concentration of an anesthetic is 0.003 moles/kg dry membrane, the anesthetic occupying a volume of 0.02% in the membrane phase. Under conditions of local anesthesia the membrane concentration is 0.04 moles/kg membrane, with an occupying volume of 0.3% in the membrane. The partitioning into the membrane is about 1/10 that of olive oil and about ⅕ that of octanol. These figures hold for many nerve-blocking drugs, and in order to explain differences in the in vivo action of these drugs, other factors must be considered, such as anesthetic sensitization etc. The biomembranes expand or swell about 10 times more than the anesthetic volume of occupation in the membrane, 0.4% expansion occuring under conditions of general anesthesia, and 2 to 3% expansion occuring under conditions of local anesthesia. Although the anesthetics electrically stabilize the membrane, they fluidize and disorder the components within the membrane, probably including membrane water. As a consequence of membrane expansion, membrane-associated enzymes and proteins can be either stimulated or inhibited. The pathways for facilitated fluxes of solutes across membranes are invariably depressed, presumably because of the conformation changes brought about by the membrane-expanding anesthetics; the Na+-conductance channel of the action potential appears to be one of these facilitated pathways. The anesthetic amines displace membrane-bound Ca++ and generally depress passive fluxes of cations. The neutral anesthetics generally increase membrane-bound Ca++ and generally increase the passive fluxes. The membrane fluidization may explain the enhanced neurosecretion of membrane-bound materials, by a mechanism of membrane-membrane fusion.
2,146 citations
TL;DR: H2-receptor antagonist, a new group of drugs, may help to unravel the physiology of histamine and gastrin.
Abstract: H2-receptor antagonist, a new group of drugs, may help to unravel the physiology of histamine and gastrin.
2,135 citations
Book•
01 Jan 1973
TL;DR: Books and internet are the recommended media to help you improving your quality and performance.
Abstract: Inevitably, reading is one of the requirements to be undergone. To improve the performance and quality, someone needs to have something new every day. It will suggest you to have more inspirations, then. However, the needs of inspirations will make you searching for some sources. Even from the other people experience, internet, and many books. Books and internet are the recommended media to help you improving your quality and performance.
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