Sandbox Reserved 1174: Difference between revisions

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[[Image:LPA.png|220px|left|thumb|'''Figure 1:''' Chemical Structure of LPA (monoacyl-sn-glycero-3-phosphate)]]

Lysophosphatidic Acid (LPA) consists of an unsaturated fatty acid chain, a glycerol backbone, and a free phosphate group (Figure 1). Lysophosphatidic acid is found in nearly all cells, tissues, and fluids of the body. LPA is present intracellularly as a precursor of phospholipid biosynthesis, and extracellularly as a signalling phospholipid~~. This page will focus on the signalling role of LPA~~.

Lysophosphatidic Acid (LPA) consists of an unsaturated fatty acid chain, a glycerol backbone, and a free phosphate group (Figure 1). Lysophosphatidic acid is found in nearly all cells, tissues, and fluids of the body. LPA is present intracellularly as a precursor of phospholipid biosynthesis, and extracellularly as a signalling phospholipid.

Extracellularly, LPA is produced from lysophosphatidylcholine by the enzyme autotaxin. Autotaxin was originally linked with metastasis, and this link was later discovered to be mediated through the production of LPA, which signals cell proliferation.<ref name= "Boutin"> DOI: 10.1007/s00018-009-0056-9 </ref> All of LPA’s activities are receptor mediated; the signalling lipid interacts with at least six G-protein coupled receptors LPA1-LPA6.

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== Function ==

Of the six LPA G-protein coupled receptors, LPA1 is the most widely expressed.<ref name= "Mills"/> ~~Lysophosphatidic acid receptor~~ 1 is coupled to a heterotrimeric G protein on the intracellular side of the cell membrane. The three G alpha proteins that LPA1 couples to are Gi, Gq, and G12/13.<ref name= "Moolenaar"> DOI: 10.1002/bies.20081 </ref> From these three G proteins many signal transduction pathways are activated. The downstream effects of Gi include cell proliferation, survival, and migration. Gi leads to cell proliferation by the activation of the RAS-mediated MAPK cascade. <ref name= "Mills"> DOI:10.1038/nrc1143 </ref> The alpha subunit Gq signals the inhibition of gap-junctional communication. The pathways activated by G12/13 include cell proliferation and morphology. These downstream functions show the wide array of effects that LPA can have on the body. Targeted deletion of LPA receptors has had an effect on every organ system examined.<ref name= "Chrencik"> DOI: 10.1016/j.cell.2015.06.002 </ref>

Of the six LPA G-protein coupled receptors, Lysophosphatidic acid recptor 1 (LPA1) is the most widely expressed.<ref name= "Mills"/> LPA,1 is coupled to a heterotrimeric G protein on the intracellular side of the cell membrane. The three G alpha proteins that LPA1 couples to are Gi, Gq, and G12/13.<ref name= "Moolenaar"> DOI: 10.1002/bies.20081 </ref> From these three G proteins many signal transduction pathways are activated. The downstream effects of Gi include cell proliferation, survival, and migration. Gi leads to cell proliferation by the activation of the RAS-mediated MAPK cascade. <ref name= "Mills"> DOI:10.1038/nrc1143 </ref> The alpha subunit Gq signals the inhibition of gap-junctional communication. The pathways activated by G12/13 include cell proliferation and morphology. These downstream functions show the wide array of effects that LPA can have on the body. Targeted deletion of LPA receptors has had an effect on every organ system examined.<ref name= "Chrencik"> DOI: 10.1016/j.cell.2015.06.002 </ref>

LPA1 is part of the larger EDG (endothelial differentiation gene) family which includes the sphingosine 1-phosphate receptors. Significantly more research has been done on S1P1 than other receptors in this family. S1P1 is coupled to the same heterotrimeric G protein that LPA1 is, and both receptors are involved in growth-related activity and cytoskeletal functions. <ref name= "Joetzl" > PMID:9837849 </ref>

Sandbox Reserved 1174: Difference between revisions

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@@ Line 6: / Line 6: @@
 [[Image:LPA.png|220px|left|thumb|'''Figure 1:''' Chemical Structure of LPA (monoacyl-sn-glycero-3-phosphate)]]
-Lysophosphatidic Acid (LPA) consists of an unsaturated fatty acid chain, a glycerol backbone, and a free phosphate group (Figure 1). Lysophosphatidic acid is found in nearly all cells, tissues, and fluids of the body. LPA is present intracellularly as a precursor of phospholipid biosynthesis, and extracellularly as a signalling phospholipid. This page will focus on the signalling role of LPA.
+Lysophosphatidic Acid (LPA) consists of an unsaturated fatty acid chain, a glycerol backbone, and a free phosphate group (Figure 1). Lysophosphatidic acid is found in nearly all cells, tissues, and fluids of the body. LPA is present intracellularly as a precursor of phospholipid biosynthesis, and extracellularly as a signalling phospholipid.
 Extracellularly, LPA is produced from lysophosphatidylcholine by the enzyme autotaxin. Autotaxin was originally linked with metastasis, and this link was later discovered to be mediated through the production of LPA, which signals cell proliferation.<ref name= "Boutin"> DOI: 10.1007/s00018-009-0056-9 </ref> All of LPA’s activities are receptor mediated; the signalling lipid interacts with at least six G-protein coupled receptors LPA<sub>1</sub>-LPA<sub>6</sub>.
@@ Line 16: / Line 16: @@
 == Function ==
-Of the six LPA G-protein coupled receptors, LPA<sub>1</sub> is the most widely expressed.<ref name= "Mills"/> Lysophosphatidic acid receptor 1 is coupled to a heterotrimeric G protein on the intracellular side of the cell membrane. The three G alpha proteins that LPA<sub>1</sub> couples to are G<sub>i</sub>, G<sub>q</sub>, and G<sub>12/13</sub>.<ref name= "Moolenaar"> DOI: 10.1002/bies.20081 </ref> From these three G proteins many signal transduction pathways are activated. The downstream effects of G<sub>i</sub> include cell proliferation, survival, and migration. G<sub>i</sub> leads to cell proliferation by the activation of the RAS-mediated MAPK cascade. <ref name= "Mills"> DOI:10.1038/nrc1143 </ref> The alpha subunit G<sub>q</sub> signals the inhibition of gap-junctional communication. The pathways activated by G<sub>12/13</sub> include cell proliferation and morphology. These downstream functions show the wide array of effects that LPA can have on the body. Targeted deletion of LPA receptors has had an effect on every organ system examined.<ref name= "Chrencik"> DOI: 10.1016/j.cell.2015.06.002 </ref>
+Of the six LPA G-protein coupled receptors, Lysophosphatidic acid recptor 1 (LPA<sub>1</sub>) is the most widely expressed.<ref name= "Mills"/> LPA,<sub>1</sub> is coupled to a heterotrimeric G protein on the intracellular side of the cell membrane. The three G alpha proteins that LPA<sub>1</sub> couples to are G<sub>i</sub>, G<sub>q</sub>, and G<sub>12/13</sub>.<ref name= "Moolenaar"> DOI: 10.1002/bies.20081 </ref> From these three G proteins many signal transduction pathways are activated. The downstream effects of G<sub>i</sub> include cell proliferation, survival, and migration. G<sub>i</sub> leads to cell proliferation by the activation of the RAS-mediated MAPK cascade. <ref name= "Mills"> DOI:10.1038/nrc1143 </ref> The alpha subunit G<sub>q</sub> signals the inhibition of gap-junctional communication. The pathways activated by G<sub>12/13</sub> include cell proliferation and morphology. These downstream functions show the wide array of effects that LPA can have on the body. Targeted deletion of LPA receptors has had an effect on every organ system examined.<ref name= "Chrencik"> DOI: 10.1016/j.cell.2015.06.002 </ref>
 LPA<sub>1</sub> is part of the larger EDG (endothelial differentiation gene) family which includes the sphingosine 1-phosphate receptors. Significantly more research has been done on S1P<sub>1</sub> than other receptors in this family. S1P<sub>1</sub> is coupled to the same heterotrimeric G protein that LPA<sub>1</sub> is, and both receptors are involved in growth-related activity and cytoskeletal functions. <ref name= "Joetzl" > PMID:9837849 </ref>