Sandbox Reserved 1175

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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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1 Human Lysophosphatodic Acid Receptor 1
2 Lysophosphatodic Acid
3 Function
4 Structure
5 References

Human Lysophosphatodic Acid Receptor 1

Lysophosphatodic Acid

Figure 1: Chemical Structure of LPA

Function

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. Another use of LPA is it can help in stimulation of cell migration ^[1].

Structure

1 Comparison of S1P and LPA
2 Function
3 Relevance
4 Clinical Testing
- 4.1 Pain

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. After an injury occurs LPA is released in the body. It then will activate G-protein-coupled receptors. Mice without the LPA₁ receptors were studied to see the role that LPA signaling played in controlling pain. 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 2: / Line 2: @@
 ==Human ''Lysophosphatodic Acid'' Receptor 1==
-<StructureSection load='4z34' size='340' side='right' caption='LPA' scene=''>
 ==Lysophosphatodic Acid==
@@ Line 9: / Line 8: @@
 ==Function==
 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.  Another use of LPA is it can help in stimulation of cell migration <ref name="Moolenaar"> DOI: 10.1002/bies.20081 </ref>.
-== Structure ==
 <scene name='72/721546/Lpa-helices/1'>Helices</scene>
+==Structure==
+<StructureSection load='4z34' size='340' side='right' caption='LPA' scene=''>
 ===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 LPA<sub>1</sub> and S1P<sub>1</sub> are known in the EDG family, comparisons are made between the two structures <ref name= "Chrencik"> PMID: 26091040 </ref>.

Sandbox Reserved 1175

From Proteopedia

Revision as of 11:59, 29 March 2016

Contents

Human Lysophosphatodic Acid Receptor 1

Lysophosphatodic Acid

Function

Structure

Contents

Comparison of S1P and LPA

Function

Relevance

Clinical Testing

Pain

References

Views

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