LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPAR1, LPAR2, and LPAR3 (also known as EDG2, EDG4, and EDG7). Additional, newly identified LPA receptors include LPAR4 (P2RY9, GPR23), LPAR5 (GPR92) and LPAR6 (P2RY5, GPR87).
Clinical significanceedit
Because of its ability to stimulate cell proliferation, aberrant LPA-signaling has been linked to cancer in numerous ways. Dysregulation of autotaxin or the LPA receptors can lead to hyperproliferation, which may contribute to oncogenesis and metastasis.[5]
LPA may be the cause of pruritus (itching) in individuals with cholestatic (impaired bile flow) diseases.
GTPase activationedit
Downstream of LPA receptor activation, the small GTPase Rho can be activated, subsequently activating Rho kinase. This can lead to the formation of stress fibers and cell migration through the inhibition of myosin light-chain phosphatase.
^van Corven, Emile J.; Groenink, Alida; Jalink, Kees; Eichholtz, Thomas; Moolenaar, Wouter H. (1989-10-06). "Lysophosphatidate-induced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins". Cell. 59 (1): 45–54. doi:10.1016/0092-8674(89)90868-4. PMID 2551506. S2CID 25154850.
^Tsukahara, Tamotsu; Tsukahara, Ryoko; Haniu, Hisao; Matsuda, Yoshikazu; Murakami-Murofushi, Kimiko (2015-09-05). "Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma". Molecular and Cellular Endocrinology. 412: 320–329. doi:10.1016/j.mce.2015.05.021. hdl:10069/35888. ISSN 0303-7207. PMID 26007326. S2CID 10454566.
^Moolenaar, Wouter H. (1995-06-02). "Lysophosphatidic Acid, a Multifunctional Phospholipid Messenger ∗". Journal of Biological Chemistry. 270 (22): 12949–12952. doi:10.1074/jbc.270.22.12949. ISSN 0021-9258. PMID 7768880.
^Tigyi, Gabor; Parrill, Abby L. (2003-11-01). "Molecular mechanisms of lysophosphatidic acid action". Progress in Lipid Research. 42 (6): 498–526. doi:10.1016/S0163-7827(03)00035-3. ISSN 0163-7827. PMID 14559069.
^Benesch, MG; Ko, YM; McMullen, TP; Brindley, DN (2014). "Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions". FEBS Letters. 588 (16): 2712–27. doi:10.1016/j.febslet.2014.02.009. PMID 24560789. S2CID 35544825.
Further readingedit
Kremer, Andreas E.; Martens, Job J.W.W.; Kulik, Wim; Ruëff, Franziska; Kuiper, Edith M.M.; Van Buuren, Henk R.; Van Erpecum, Karel J.; Kondrackiene, Jurate; et al. (2010). "Lysophosphatidic Acid is a Potential Mediator of Cholestatic Pruritus". Gastroenterology. 139 (3): 1008–18, 1018.e1. doi:10.1053/j.gastro.2010.05.009. PMID 20546739.
Moolenaar, Wouter H. (1995). "Lysophosphatidic Acid, a Multifunctional Phospholipid Messenger". The Journal of Biological Chemistry. 270 (22): 12949–52. doi:10.1074/jbc.270.22.12949. PMID 7768880.
Mills, Gordon B.; Moolenaar, Wouter H. (2003). "The emerging role of lysophosphatidic acid in cancer". Nature Reviews Cancer. 3 (8): 582–91. doi:10.1038/nrc1143. PMID 12894246. S2CID 29079135.
Panupinthu, N; Lee, H Y; Mills, G B (2010). "Lysophosphatidic acid production and action: Critical new players in breast cancer initiation and progression". British Journal of Cancer. 102 (6): 941–6. doi:10.1038/sj.bjc.6605588. PMC2844037. PMID 20234370.
Park, S Y; Jeong, K J; Panupinthu, N; Yu, S; Lee, J; Han, J W; Kim, J M; Lee, J-S; et al. (2010). "Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression". Oncogene. 30 (11): 1351–9. doi:10.1038/onc.2010.517. PMID 21102517.
Yakubu, M A; Liliom, K; Tigyi, G J; Leffler, C W (1997). "Role of lysophosphatidic acid in endothelin-1-and hematoma-induced alteration of cerebral microcirculation". 273 (2): R703–R709. doi:10.1152/ajpregu.1997.273.2.R703. {{cite journal}}: Cite journal requires |journal= (help)
Tigyi, G J; Hong, L; Yakubu, M; Parfenova, H; Shibata, M; Leffler, C W (1995). "Lysophosphatidic acid alters cerebrovascular reactivity in piglets". 268 (5): H2048–H2055. doi:10.1152/ajpheart.1995.268.5.H2048. {{cite journal}}: Cite journal requires |journal= (help)
December 14, 2023
lysophosphatidic, acid, lysophosphatidic, acid, phospholipid, derivative, that, signaling, molecule, namessystematic, iupac, name, hydroxy, octadec, enoyl, propyl, dihydrogen, phosphateother, names, lpa1, acyl, glycerol, phosphateidentifierscas, number, 22002,. A lysophosphatidic acid LPA is a phospholipid derivative that can act as a signaling molecule 1 2 3 4 Lysophosphatidic acid NamesSystematic IUPAC name 2R 2 hydroxy 3 9Z octadec 9 enoyl oxy propyl dihydrogen phosphateOther names LPA1 acyl sn glycerol 3 phosphateIdentifiersCAS Number 22002 87 5 Y3D model JSmol Interactive imageChEMBL ChEMBL117021 NChemSpider 4593722ECHA InfoCard 100 040 631EC Number 244 710 0IUPHAR BPS 2906MeSH lysophosphatidic acidPubChem CID 5497152UNII PG6M3969SG YCompTox Dashboard EPA DTXSID5041061InChI InChI 1S C21H41O7P c1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 21 23 27 18 20 22 19 28 29 24 25 26 h9 10 20 22H 2 8 11 19H2 1H3 H2 24 25 26 b10 9 Key WRGQSWVCFNIUNZ KTKRTIGZSA NSMILES CCCCCCCC C C CCCCCCCC O OCC COP O O O OPropertiesChemical formula C21H41O7PMolar mass 436 52 g molExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references Contents 1 Function 2 Clinical significance 3 GTPase activation 4 Metabolism 5 See also 6 References 7 Further readingFunction editSee also Lysophospholipid receptor LPA acts as a potent mitogen due to its activation of three high affinity G protein coupled receptors called LPAR1 LPAR2 and LPAR3 also known as EDG2 EDG4 and EDG7 Additional newly identified LPA receptors include LPAR4 P2RY9 GPR23 LPAR5 GPR92 and LPAR6 P2RY5 GPR87 Clinical significance editBecause of its ability to stimulate cell proliferation aberrant LPA signaling has been linked to cancer in numerous ways Dysregulation of autotaxin or the LPA receptors can lead to hyperproliferation which may contribute to oncogenesis and metastasis 5 LPA may be the cause of pruritus itching in individuals with cholestatic impaired bile flow diseases GTPase activation editDownstream of LPA receptor activation the small GTPase Rho can be activated subsequently activating Rho kinase This can lead to the formation of stress fibers and cell migration through the inhibition of myosin light chain phosphatase Metabolism editThere are a number of potential routes to its biosynthesis but the most well characterized is by the action of a lysophospholipase D called autotaxin which removes the choline group from lysophosphatidylcholine Lysophosphatidic acids are also intermediates in the synthesis of phosphatidic acids nbsp See also editAutotaxin GPR35 Phosphatidic acid Sphingosine 1 phosphate GintoninReferences edit van Corven Emile J Groenink Alida Jalink Kees Eichholtz Thomas Moolenaar Wouter H 1989 10 06 Lysophosphatidate induced cell proliferation Identification and dissection of signaling pathways mediated by G proteins Cell 59 1 45 54 doi 10 1016 0092 8674 89 90868 4 PMID 2551506 S2CID 25154850 Tsukahara Tamotsu Tsukahara Ryoko Haniu Hisao Matsuda Yoshikazu Murakami Murofushi Kimiko 2015 09 05 Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator activated receptor gamma Molecular and Cellular Endocrinology 412 320 329 doi 10 1016 j mce 2015 05 021 hdl 10069 35888 ISSN 0303 7207 PMID 26007326 S2CID 10454566 Moolenaar Wouter H 1995 06 02 Lysophosphatidic Acid a Multifunctional Phospholipid Messenger Journal of Biological Chemistry 270 22 12949 12952 doi 10 1074 jbc 270 22 12949 ISSN 0021 9258 PMID 7768880 Tigyi Gabor Parrill Abby L 2003 11 01 Molecular mechanisms of lysophosphatidic acid action Progress in Lipid Research 42 6 498 526 doi 10 1016 S0163 7827 03 00035 3 ISSN 0163 7827 PMID 14559069 Benesch MG Ko YM McMullen TP Brindley DN 2014 Autotaxin in the crosshairs taking aim at cancer and other inflammatory conditions FEBS Letters 588 16 2712 27 doi 10 1016 j febslet 2014 02 009 PMID 24560789 S2CID 35544825 Further reading editKremer Andreas E Martens Job J W W Kulik Wim Rueff Franziska Kuiper Edith M M Van Buuren Henk R Van Erpecum Karel J Kondrackiene Jurate et al 2010 Lysophosphatidic Acid is a Potential Mediator of Cholestatic Pruritus Gastroenterology 139 3 1008 18 1018 e1 doi 10 1053 j gastro 2010 05 009 PMID 20546739 Moolenaar Wouter H 1995 Lysophosphatidic Acid a Multifunctional Phospholipid Messenger The Journal of Biological Chemistry 270 22 12949 52 doi 10 1074 jbc 270 22 12949 PMID 7768880 Mills Gordon B Moolenaar Wouter H 2003 The emerging role of lysophosphatidic acid in cancer Nature Reviews Cancer 3 8 582 91 doi 10 1038 nrc1143 PMID 12894246 S2CID 29079135 Panupinthu N Lee H Y Mills G B 2010 Lysophosphatidic acid production and action Critical new players in breast cancer initiation and progression British Journal of Cancer 102 6 941 6 doi 10 1038 sj bjc 6605588 PMC 2844037 PMID 20234370 Park S Y Jeong K J Panupinthu N Yu S Lee J Han J W Kim J M Lee J S et al 2010 Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP 9 expression Oncogene 30 11 1351 9 doi 10 1038 onc 2010 517 PMID 21102517 Yakubu M A Liliom K Tigyi G J Leffler C W 1997 Role of lysophosphatidic acid in endothelin 1 and hematoma induced alteration of cerebral microcirculation 273 2 R703 R709 doi 10 1152 ajpregu 1997 273 2 R703 a href Template Cite journal html title Template Cite journal cite journal a Cite journal requires journal help Tigyi G J Hong L Yakubu M Parfenova H Shibata M Leffler C W 1995 Lysophosphatidic acid alters cerebrovascular reactivity in piglets 268 5 H2048 H2055 doi 10 1152 ajpheart 1995 268 5 H2048 a href Template Cite journal html title Template Cite journal cite journal a Cite journal requires journal help Retrieved from https en wikipedia org w index php title Lysophosphatidic acid amp oldid 1153068310, wikipedia, wiki, book, books, library,
