Lysophosphatidic acid LPA

Westermann AM, Havik E, Postma FR, Beijnen JH, Dalesio O, Moolenaar WH, Roden-huis S (1998) Malignant effusions contain lysophosphatidic acid (LPA)-like activity. Ann Oncol 9 437-442... 

Messenger substances derived from phospholipids can also function as hormones and serve for communication between cells. An important extracellular messenger substance formed from phospholipids is lysophosphatidic acid (l-acyl-sn-glycerine-3-phos-phate). Lysophosphatidic acid (lysophosphatidic acid, LPA) is released by platelets and other cells and reaches its target cells via the circulation. As a product of the blood clotting process, LPA is an abimdant constituent of serum, where it is found in an albu-min-boimd form. 

Figure 21-3 Major pathways of synthesis of fatty acids and glycerolipids in the green plant Arabidopsis. The major site of fatty acid synthesis is chloroplasts. Most is exported to the cytosol as oleic acid (18 1). After conversion to its coenzyme A derivative it is converted to phosphatidic acid (PA), diacylglycerol (DAG), and the phospholipids phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). Desaturation also occurs, and some linoleic and linolenic acids are returned to the chloroplasts. See text also. From Sommerville and Browse.106 See also Figs. 21-4 and 21-5. Other abbreviations monogalactosyldiacylglycerol (MGD), digalactosyldiacylglycerol (DGD), sulfolipid (SL), glycerol 3-phosphate (G3P), lysophosphatidic acid (LPA), acyl carrier protein (ACP), cytidine diphosphate-DAG (CDP-DAG).

As in the case of anandamide, 2-AG is derived from the hydrolysis of complex membrane lipids. The direct precursors of 2-AG can either be 1-acyl, 2-arachidonoyl-diacylglycerols (DAGs) or 2-arachidonoyl-lysoglycerophospholi-pids (e.g., lysophosphatidic acid, LPA). 

Much attention has recently focused on lyso-formed phospholipids, including both glycerophospho-lipids such as lysophosphatidic acid (LPA) and lysosphingolipids such as sphingosine-1-phosphate (S-l-P) and sphingosylphosphorylcholine (SPC) (Figure 27.2), since they elicit diverse cellular... 

Each new preparation of C3 protein is also assayed by microinjection into quiescent serum-starved Swiss 3T3 cells, followed by treatment with lysophosphatidic acid, LPA (lOOng/ml for 15 or 30 min Sigma L7260) to stimulate Rho and stress fibre assembly (see Section 6.6). The lowest concentration of C3 that still blocks the LPA effect provides a measure of the relative activity of different batches of C3. 

In mammalian systems, PLD has been suggested to play roles in growth and differentiation, secretion, vesicle trafficking and transport, cytoskeletal rearrangements, superoxide production in phagocytes, protein translation and the production of lysophosphatidic acid (LPA). 

Eder AM, Sasagawa T, Mao M, Aoki J, Mills GB (2000) Constitutive and lysophosphatidic acid (LPA)-induced LPA production role of phospholipase D and phospholipase A2. Clin Cancer Res 6 2482-2491... 

Fukushima N, Weiner JA, Chun J (2000) Lysophosphatidic acid (LPA) is a novel extracellular regulator of cortical neuroblast morphology. Dev Biol 228 6-18... 

The roles of Ras-related proteins were revealed by simple microinjectlon experiments. When Rac was mlcroln-jected into a fibroblast, the membrane immediately started to form upward projections called ruffles focal adhesions and stress fibers formed 5-10 minutes later. Injection of an inactive form of Rac inhibited all reorganization of the actin cytoskeleton when growth factors were added to the cell. When Rho, rather than Rac, was injected, it mimicked the mitogenic effects of lysophosphatidic acid (LPA), a chemokine in serum and a potent stimulator of platelet aggregation. Both Rho and LPA induced the assembly of stress fibers and focal adhesions within 2 minutes but did not induce membrane ruffling. 

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