Sandbox Reserved 1172: Difference between revisions
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== Introduction == | == Introduction == | ||
Lysophosphatidic Acid Receptor 1 (commonly referred to as LPA<sub>1</sub>) is a [[G protein-coupled receptor]] and one of 6 different LPA receptors (LPA<sub>1</sub>-LPA<sub>6</sub>). These receptors bind the phospholipid derivative [https://en.wikipedia.org/wiki/Lysophosphatidic_acid lysophosphatidic acid (LPA)], a signaling molecule that acts as a potent [https://en.wikipedia.org/wiki/Mitogen mitogen] upon binding to one of its six receptors.<ref name="regpeps">PMID: 26091040</ref> LPA<sub>1</sub> is part of the larger [http://jb.oxfordjournals.org/content/131/6/767 EDG receptor family], which includes the more widely studied sphingosine 1-phopshate receptors. This receptor is responsible for initiating signaling cascades that result in growth, survival, and movement of cells, as well as neural cell development. | Lysophosphatidic Acid Receptor 1 (commonly referred to as LPA<sub>1</sub>) is a [[G protein-coupled receptor]] and one of 6 different LPA receptors (LPA<sub>1</sub>-LPA<sub>6</sub>). These receptors bind the phospholipid derivative [https://en.wikipedia.org/wiki/Lysophosphatidic_acid lysophosphatidic acid (LPA)], a signaling molecule that acts as a potent [https://en.wikipedia.org/wiki/Mitogen mitogen] upon binding to one of its six receptors.<ref name="regpeps">PMID: 26091040</ref> LPA<sub>1</sub> is part of the larger [http://jb.oxfordjournals.org/content/131/6/767 EDG receptor family], which includes the more widely studied sphingosine 1-phopshate receptors.<ref name="regpeps">PMID: 26091040</ref> This receptor is responsible for initiating signaling cascades that result in growth, survival, and movement of cells, as well as neural cell development. | ||
== Structure == | == Structure == | ||
[[Image:Pic2proteo3.png|275 px|left|thumb|Figure 1: Surface representation of the LPA<sub>1</sub> receptor in tan interacting with its antagonist, ON7, shown in green and red sticks.The exterior of the protein was partially cut away to display the interior binding pocket.]] | [[Image:Pic2proteo3.png|275 px|left|thumb|Figure 1: Surface representation of the LPA<sub>1</sub> receptor in tan interacting with its antagonist, ON7, shown in green and red sticks.The exterior of the protein was partially cut away to display the interior binding pocket.]] | ||
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== Disease Relevance == | == Disease Relevance == | ||
Because LPA<sub>1</sub> is expressed in so many tissues throughout the body, LPA<sub>1</sub> has been linked to the symptoms and progression of several different diseases and disorders.<ref name="number6">PMID: 20331961</ref> For example, due to LPA<sub>1</sub>'s role in pain signaling, overexpression of this protein can cause both [https://en.wikipedia.org/wiki/Allodynia allodynia] or [https://en.wikipedia.org/wiki/Hyperalgesia hyperalgesia], common symptoms of multiple sclerosis or strokes.<ref name="number6">PMID: 20331961</ref> In addition, since LPA<sub>1</sub> helps in the myelination of Schwann cells, mutation of the receptor can also lead to a decrease in [https://en.wikipedia.org/wiki/Prepulse_inhibition prepulse inhibition], a general sign of schizophrenia.<ref name="number6">PMID: 20331961</ref> Lastly, because of the mitogen signaling activity of LPA<sub>1</sub>, abnormal expression or mutation of this receptor has been linked to tumor growth, survival, and migration in both liver and lung tumors. Part of this tumorigenesis can be explained by the action of <scene name='72/721543/His40/4'>His40</scene> on LPA<sub>1</sub> where, when protonated, increases LPA binding affinity by up to 1kcal/mol. Consequently, in the acidic environment produced by [https://en.wikipedia.org/wiki/Tumor_hypoxia hypoxic tumors] creating lactic acid, LPA<sub>1</sub> activity is increased, allowing these tumors to continue to proliferate, migrate, and survive.<ref name="number7">PMID: 24367336</ref> In contrast, the LPA<sub>1</sub> receptor also induces protective functions in different cardiovascular conditions. For example, in patients with heart disease, LPA<sub>1</sub> communicates with [[PI3K]], [https://en.wikipedia.org/wiki/Protein_kinase_B PKB], and [[ERK]] to create a hypertrophic response in the heart to offset reduced heart contractions. | Because LPA<sub>1</sub> is expressed in so many tissues throughout the body, LPA<sub>1</sub> has been linked to the symptoms and progression of several different diseases and disorders.<ref name="number6">PMID: 20331961</ref><ref name="number7">PMID: 24367336</ref> For example, due to LPA<sub>1</sub>'s role in pain signaling, overexpression of this protein can cause both [https://en.wikipedia.org/wiki/Allodynia allodynia] or [https://en.wikipedia.org/wiki/Hyperalgesia hyperalgesia], common symptoms of multiple sclerosis or strokes.<ref name="number6">PMID: 20331961</ref> In addition, since LPA<sub>1</sub> helps in the myelination of Schwann cells, mutation of the receptor can also lead to a decrease in [https://en.wikipedia.org/wiki/Prepulse_inhibition prepulse inhibition], a general sign of schizophrenia.<ref name="number6">PMID: 20331961</ref> Lastly, because of the mitogen signaling activity of LPA<sub>1</sub>, abnormal expression or mutation of this receptor has been linked to tumor growth, survival, and migration in both liver and lung tumors.<ref name="number7">PMID: 24367336</ref> Part of this tumorigenesis can be explained by the action of <scene name='72/721543/His40/4'>His40</scene> on LPA<sub>1</sub> where, when protonated, increases LPA binding affinity by up to 1kcal/mol.<ref name="regpeps">PMID: 26091040</ref> Consequently, in the acidic environment produced by [https://en.wikipedia.org/wiki/Tumor_hypoxia hypoxic tumors] creating lactic acid, LPA<sub>1</sub> activity is increased, allowing these tumors to continue to proliferate, migrate, and survive.<ref name="number7">PMID: 24367336</ref> In contrast, the LPA<sub>1</sub> receptor also induces protective functions in different cardiovascular conditions. For example, in patients with heart disease, LPA<sub>1</sub> communicates with [[PI3K]], [https://en.wikipedia.org/wiki/Protein_kinase_B PKB], and [[ERK]] to create a hypertrophic response in the heart to offset reduced heart contractions.<ref name="number6">PMID: 20331961</ref> | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
