Lipid signaling refers to a number of cellular signal transduction pathways that use cell membrane lipids as second messengers. Most of the lipids of the plasma membrane play an exclusively structural role. However, a small proportion of them are involved in relaying extracellular stimuli into the cell. The best studied of these pathways centres around diacylglycerol(DAG) and inositol triphosphate(IP3), which is described in detail in this article. Ceramide lipids also play in cell signaling. It has been suggested that cell signaling be merged into this article or section. ... Drawing of a cell membrane A component of every biological cell, the selectively permeable cell membrane (or plasma membrane or plasmalemma) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... Figure 1: Basic lipid structure. ... In biology, second messengers are low-weight diffusible molecules that are used in signal transduction to relay signals within a cell. ... Drawing of a cell membrane A component of every biological cell, the cell membrane (or plasma membrane) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... In cell biology, molecular biology and related fields, the word extracellular means outside the cell. It is used in contrast to intracellular (inside the cell). ... Diacylglycerol (DAG) is a second messenger molecule made by phospholipase C (a membrane-bound enzyme), together with inositol triphosphate. ... Inositol triphosphate or inositol 1,4,5-triphosphate (also commonly known as triphosphoinositol; abbreviated InsP3 or IP3), together with diacylglycerol, is a second messenger molecule used in signal transduction in biological cells. ... Ceramides are a family of lipid molecules. ... Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. ...

Function

Lipid signaling pathways are activated by a variety of extracellular stimuli ranging from growth factors to inflamatory cytokines. They regulate cell fate decisions such as apoptosis, differentiation and proliferation. Lipid signaling can play a major role in carcinogenesis, the development of cancer. Phorbol esters mimic the lipid second messenger diacylglycerol and can stimulate cancer cells to divide. Growth factor is a protein that acts as a signaling molecule between cells (like cytokines and hormones) that attaches to specific receptors on the surface of a target cell and promotes differentiation and maturation of these cells. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Cytokines are small protein molecules that regulate communication among immune system cells and between immune cells and those of other tissue types. ... A cell undergoing apoptosis. ... Differentiation can mean the following: In biology: cellular differentiation; evolutionary differentiation; In mathematics: see: derivative In cosmogony: planetary differentiation Differentiation (geology); Differentiation (logic); Differentiation (marketing). ... The word proliferation can refer to: Nuclear proliferation Chemical weapon proliferation the spread in use of other weapons systems Cell proliferation According to Gloria Anzaldúa (1990), the difference between appropriation and proliferation is that the first steals and harms; the second helps heal breaches of knowledge. ... Cancers are caused by a series of mutations. ... When normal cells are damaged beyond repair, they are eliminated by apoptosis. ... Phorbol is a natural, plant-derived organic compound. ... In biology, second messengers are low-weight diffusible molecules that are used in signal transduction to relay signals within a cell. ... Diacylglycerol (DAG) is a second messenger molecule made by phospholipase C (a membrane-bound enzyme), together with inositol triphosphate. ...

Mechanism

The key event of lipid signaling is the hydrolysis of Phosphatidylinositol (4,5)-bisphosphate to diacylglycerol(DAG) and inositol triphosphate(IP3) by the phospholipase C (PLC) enzyme. Two PLC isoforms, PLC-β activated by G proteins, and, PLC-γ activated by receptor tyrosine kinases, catalyse this reaction. Hydrolysis is a chemical process in which a molecule is split into two parts by the addition of a molecule of water. ... Chemical structure of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol 4,5-bisphosphate Phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) is a minor phospholipid component of cell membranes. ... Diacylglycerol (DAG) is a second messenger molecule made by phospholipase C (a membrane-bound enzyme), together with inositol triphosphate. ... Inositol triphosphate or inositol 1,4,5-triphosphate (also commonly known as triphosphoinositol; abbreviated InsP3 or IP3), together with diacylglycerol, is a second messenger molecule used in signal transduction in biological cells. ... A phospholipase is an enzyme that converts phospholipids into fatty acids and other lipophilic substances. ... Ribbon diagram of the enzyme TIM. TIM is catalytically perfect, meaning its conversion rate is limited, or nearly limited to its substrate diffusion rate. ...

IP3 is soluble and diffuse freely into the cytoplasm. It is recognised by the inositol triphosphate receptor(IP3R), a Ca²⁺ channel in the endoplasmic reticulum(ER) membrane. The ER acts as intracellular Ca²⁺ store. The binding of IP3 to IP3R releases the flow of calcium from the ER into the normally Ca²⁺-poor cytoplasm, which then triggers various events of calcium signaling. Ca²⁺ binds the protein calmodulin, which regulates a range of cellular targets, such as the Ca2+/calmodulin-dependent protein kinases. Intracellular Ca²⁺ is also essential for activation of conventional Protein kinase C isoforms. DAG remains bound to the membrane by its fatty acid "tails". Their it recruits and activates both conventional and novel members of the Protein kinase C family. Thus, both IP3 and DAG contribute to activation of PKCs. Inositol triphosphate receptor (IP3R) is a membrane glycoprotein complex acting as Ca2+ channel activated by inositol triphosphate (IP3). ... The endoplasmic reticulum or ER (endoplasmic means within the cytoplasm, reticulum means little net) is an organelle found in all eukaryotic cells. ... Calcium ions act as second messengers in signal transduction. ... Calmodulin 3D structure Calmodulin (CaM) is a Ca2+-binding protein that is a key component of the Ca2+ second-messenger system and is involved in controlling many of the biochemical processes of cells. ... A protein kinase is an enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). ... A protein kinase is an enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). ... In biology, a protein isoform is a version of a protein with some small differences, usually a splice variant or the product of some posttranslational modification. ... In chemistry, especially biochemistry, a fatty acid is a carboxylic acid (or organic acid), often with a long aliphatic tail (long chains), either saturated or unsaturated. ... A protein kinase is an enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). ...

Protein kinase C-α is a conventional PKC and requires both DAG and Ca²⁺ for activity. One of the targets activated by PKC-α is phospholipase D, which hydrolyses phosphatidylcholine(PC) to choline and phosphatidic acid. The latter is rapidly converted to DAG. PC-derived DAG can be distinguished from PIP2-derived as their differ in their fatty acid composition. PC forms the bulk of the lipids of the plasma membrane and provides an inexhaustible supply of substrates for PLD. DAG produces through this mechanism may continue to activate PKC hours after the initial extracellular stimulus. A phospholipase is an enzyme that converts phospholipids into fatty acids and other lipophilic substances. ... Lecithin, also known as Phosphatidylcholine Lecithin is usually used as synonym for phosphatidylcholine, a phospholipid which is the major component of a phosphatide fraction which may be isolated from either egg yolk (in Greek lekithos - λεκιθος), or soy beans. ... // Choline is a nutrient, essential for cardiovascular and brain function, and for cellular membrane composition and repair. ... In chemistry, especially biochemistry, a fatty acid is a carboxylic acid (or organic acid), often with a long aliphatic tail (long chains), either saturated or unsaturated. ...

References

General reviews

• Irvine RF (1992). "Inositol lipids in cell signalling". Curr Opin Cell Biol 4 (2): 212-219. Entrez PubMed 1318060
• Nishizuka Y (1995). "Protein kinase C and lipid signaling for sustained cellular responses". FASEB J 9 (7): 484-496. Entrez PubMed 7737456

The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ...

A phospholipase is an enzyme that converts phospholipids into fatty acids and other lipophilic substances. ... Chemical structure of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol 4,5-bisphosphate Phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) is a minor phospholipid component of cell membranes. ... Diacylglycerol (DAG) is a second messenger molecule made by phospholipase C (a membrane-bound enzyme), together with inositol triphosphate. ... Inositol triphosphate or inositol 1,4,5-triphosphate (also commonly known as triphosphoinositol; abbreviated InsP3 or IP3), together with diacylglycerol, is a second messenger molecule used in signal transduction in biological cells. ... Inositol triphosphate receptor (IP3R) is a membrane glycoprotein complex acting as Ca2+ channel activated by inositol triphosphate (IP3). ...