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This Sandbox is Reserved from Jan 11 through August 12, 2016 for use in the course CH462 Central Metabolism taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1160 through Sandbox Reserved 1184.

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Human Lysophosphatodic Acid Receptor 1

Figure 1: Chemical Structure of LPA

1 Lysophosphatodic Acid
2 Function
3 Structure
- 3.1 Comparison of S1P and LPA
4 Function
5 Relevance
6 Clinical Testing
- 6.1 Pain

Lysophosphatodic Acid

Function

Structure

Comparison of S1P and LPA

Lysophosphatidic Acid Receptors (LPA) are part of a larger family known as lysophospholipid receptor family (EDG family). Within this family there is a structure called S1P1. Since only the structures for LPA₁ and S1P₁ are known in the EDG family, comparisons are made between the two structures ^[2].

There is a difference in binding paths between these two receptors. The binding path in the LPA₁ is located in the extracellular milieu. While in the S1P₁ the ligands are able to have access to the membrane so that the binding can occur.

Figure 2: Comparison of the binding pockets of LPA₁ and S1P₁ receptors

There is a difference in the shape of the electron density from the binding pocket. In S1P₁ the binding pocket has more of an oval shape. For the LPA₁ receptor the binding pocket has a spherical shape. Since the binding pocket is more spherical it gives LPA₁ the ability to be able to recognize a larger group of chemical species. In particular the ability to bind with acyl chains of varying lengths ^[2].

Function

Relevance

Clinical Testing

LPA is still in the clinical stage of testing. So far the LPA receptors have had physiological effects on every organism that it has been tested with. There have been studies done looking at what happens with infertility, fibrosis, pain, and cancer when they come into contact with LPA receptors ,ref name= "Chrencik"/>. LPA receptors are commonly found in serum and saliva. ^[1].

Pain

LPA, a signaling phospholipid, can attach to three specific G-protein-coupled receptors. LPA can activate multiple pathways in particular, Ras and Pho which belong to the family of GTPases ^[3]. Another use of LPA is it can help in stimulation of cell migration ^[1]. It was seen that with targeted deletion of LPA receptors the mice would be cured from fibrosis. Mice who had fibrosis were given LPA1 regulated LPA-induced fibroblast. Over time the mice who had fibrosis began to have their lungs repaired. The amount of fluid in their lungs decreased.

References

↑ ^1.0 ^1.1 ^1.2 Moolenaar WH, van Meeteren LA, Giepmans BN. The ins and outs of lysophosphatidic acid signaling. Bioessays. 2004 Aug;26(8):870-81. PMID:15273989 doi:http://dx.doi.org/10.1002/bies.20081
↑ ^2.0 ^2.1 Chrencik JE, Roth CB, Terakado M, Kurata H, Omi R, Kihara Y, Warshaviak D, Nakade S, Asmar-Rovira G, Mileni M, Mizuno H, Griffith MT, Rodgers C, Han GW, Velasquez J, Chun J, Stevens RC, Hanson MA. Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1. Cell. 2015 Jun 18;161(7):1633-43. doi: 10.1016/j.cell.2015.06.002. PMID:26091040 doi:http://dx.doi.org/10.1016/j.cell.2015.06.002
↑ Inoue M, Rashid MH, Fujita R, Contos JJ, Chun J, Ueda H. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat Med. 2004 Jul;10(7):712-8. Epub 2004 Jun 13. PMID:15195086 doi:http://dx.doi.org/10.1038/nm1060

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_Reserved_1175"

@@ Line 20: / Line 20: @@
 ==Clinical Testing==
-LPA is still in the clinical stage of testing.  So far the LPA receptors have had physiological effects on every organism that it has been tested with.  There have been studies done looking at what happens with infertility, fibrosis, pain, and cancer when they come into contact with LPA receptors.  LPA receptors are commonly found in serum and saliva. <ref name= "Moolenaar"/>.
+LPA is still in the clinical stage of testing.  So far the LPA receptors have had physiological effects on every organism that it has been tested with.  There have been studies done looking at what happens with infertility, fibrosis, pain, and cancer when they come into contact with LPA receptors ,ref name= "Chrencik"/>.  LPA receptors are commonly found in serum and saliva. <ref name= "Moolenaar"/>.
 ===Pain===
-Since LPA receptors are present in the nervous system, they are able to help manage neuropathic pain <ref name= "Inoue"> DOI:10.1038/nm1060 </ref>.
+LPA, a signaling phospholipid, can attach to three specific G-protein-coupled receptors.  LPA can activate multiple pathways in particular, Ras and Pho which belong to the family of GTPases <ref name= "Inoue"> DOI:10.1038/nm1060 </ref>.  Another use of LPA is it can help in stimulation of cell migration <ref name= "Moolenaar" </ref>.
-===Cancer===
+===Fibrosis===
-To look at the effects of LPA on cancer, there was a study done with mice <ref> PMID:18066075 </ref>.  It was seen that when in the presence of LPA1 receptors the mice would not contract fibrosis.  Mice who had fibrosis were given LPA1 regulated LPA-induced fibroblast.  Over time the mice who had fibrosis began to have their lungs repaired.  The amount of fluid in their lungs decreased.
+To look at the effects of LPA on fibrosis, there was a study done with mice <ref> PMID:18066075 </ref>.  It was seen that with targeted deletion of LPA receptors the mice would be cured from fibrosis.  Mice who had fibrosis were given LPA1 regulated LPA-induced fibroblast.  Over time the mice who had fibrosis began to have their lungs repaired.  The amount of fluid in their lungs decreased.
 </StructureSection>
 == References ==
 <references/>

Sandbox Reserved 1175

From Proteopedia

Revision as of 06:48, 29 March 2016

Human Lysophosphatodic Acid Receptor 1

Contents

Lysophosphatodic Acid

Function

Structure

Comparison of S1P and LPA

Function

Relevance

Clinical Testing

Pain

References

Views

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