lysophosphatidic acid receptors

Summary

Summary: A subfamily of lysophospholipid receptors with specificity for LYSOPHOSPHATIDIC ACIDS.

Top Publications

  1. Murakami M, Shiraishi A, Tabata K, Fujita N. Identification of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor. Biochem Biophys Res Commun. 2008;371:707-12 pubmed publisher
    ..In conclusion, the P2Y(10) receptor is the first receptor identified as a dual lysophospholipid receptor. ..
  2. Inoue M, Ma L, Aoki J, Ueda H. Simultaneous stimulation of spinal NK1 and NMDA receptors produces LPC which undergoes ATX-mediated conversion to LPA, an initiator of neuropathic pain. J Neurochem. 2008;107:1556-65 pubmed publisher
    ..These findings suggest that simultaneous intense stimulation of neurokinin 1 and NMDA receptors in the spinal dorsal horn triggers lysophosphatidic acid production from lysophosphatidylcholine through extracellular autotaxin. ..
  3. Goetzl E, Dolezalova H, Kong Y, Zeng L. Dual mechanisms for lysophospholipid induction of proliferation of human breast carcinoma cells. Cancer Res. 1999;59:4732-7 pubmed
    ..Edg Rs thus transduce LPA and S1P enhancement of BCC growth, both directly through SRE and indirectly by enhancing the contribution of IGF-II. ..
  4. Goetzl E, Dolezalova H, Kong Y, Hu Y, Jaffe R, Kalli K, et al. Distinctive expression and functions of the type 4 endothelial differentiation gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian cancer. Cancer Res. 1999;59:5370-5 pubmed
    ..Thus the Edg-4 R may represent a distinctive marker of OCC that transduces growth-promoting signals from the high local concentrations of LPA characteristic of aggressive ovarian cancer. ..
  5. Fukushima N, Ye X, Chun J. Neurobiology of lysophosphatidic acid signaling. Neuroscientist. 2002;8:540-50 pubmed
    ..Here the authors review features of the LPA receptor family and cellular responses of nervous system-derived cells, and discuss developmental and pathological roles for LPA signaling in the nervous system. ..
  6. van Meeteren L, Moolenaar W. Regulation and biological activities of the autotaxin-LPA axis. Prog Lipid Res. 2007;46:145-60 pubmed
  7. Mills G, Moolenaar W. The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer. 2003;3:582-91 pubmed
  8. Moolenaar W. Bioactive lysophospholipids and their G protein-coupled receptors. Exp Cell Res. 1999;253:230-8 pubmed
    ..A major recent advance is the identification of a subfamily of heptahelical receptors for LPA and S1P. ..
  9. Ptaszynska M, Pendrak M, Stracke M, Roberts D. Autotaxin signaling via lysophosphatidic acid receptors contributes to vascular endothelial growth factor-induced endothelial cell migration. Mol Cancer Res. 2010;8:309-21 pubmed publisher
    ..These data further suggest that ATX could be a prognostic factor or a target for therapeutic intervention in several cancers. ..

More Information

Publications62

  1. Urs N, Jones K, Salo P, Severin J, Trejo J, Radhakrishna H. A requirement for membrane cholesterol in the beta-arrestin- and clathrin-dependent endocytosis of LPA1 lysophosphatidic acid receptors. J Cell Sci. 2005;118:5291-304 pubmed
    ..These data indicate that although LPA(1) is internalized by clathrin- and beta-arrestin dependent endocytosis, membrane cholesterol is critical for LPA(1) signaling, membrane recruitment of beta-arrestins and LPA(1) endocytosis. ..
  2. Kostenis E. Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for "old" ligands. J Cell Biochem. 2004;92:923-36 pubmed
    ..Recently deorphaned lipid receptors, within and outside the known lipid receptor clusters will receive particular attention. ..
  3. Fukushima N, Kimura Y, Chun J. A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid. Proc Natl Acad Sci U S A. 1998;95:6151-6 pubmed
    ..These results demonstrate that a single receptor, encoded by vzg-1, can activate multiple LPA-dependent responses in cells from distinct tissue lineages. ..
  4. An S, Bleu T, Hallmark O, Goetzl E. Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J Biol Chem. 1998;273:7906-10 pubmed
    ..The existence and distinctive tissue expression of structurally different subtypes of LPA receptors may provide one basis for tissue-specific functions and permit independent regulation of each subtype of LPA receptor. ..
  5. Moller T, Contos J, Musante D, Chun J, Ransom B. Expression and function of lysophosphatidic acid receptors in cultured rodent microglial cells. J Biol Chem. 2001;276:25946-52 pubmed
    ..Our findings provide evidence for functional LPA receptors on microglia. Thus, LPA might play an important role as a mediator of microglial activation in response to central nervous system injury. ..
  6. Horak C, Mendoza A, Vega Valle E, Albaugh M, Graff Cherry C, McDermott W, et al. Nm23-H1 suppresses metastasis by inhibiting expression of the lysophosphatidic acid receptor EDG2. Cancer Res. 2007;67:11751-9 pubmed
    ..73; P = 0.004). The data indicate that Nm23-H1 down-regulation of EDG2 is functionally important to suppression of tumor metastasis. ..
  7. Kingsbury M, Rehen S, Contos J, Higgins C, Chun J. Non-proliferative effects of lysophosphatidic acid enhance cortical growth and folding. Nat Neurosci. 2003;6:1292-9 pubmed
    ..Our results implicate extracellular lipid signals as new influences on brain formation during embryonic development. ..
  8. Fukushima N, Ishii I, Habara Y, Allen C, Chun J. Dual regulation of actin rearrangement through lysophosphatidic acid receptor in neuroblast cell lines: actin depolymerization by Ca(2+)-alpha-actinin and polymerization by rho. Mol Biol Cell. 2002;13:2692-705 pubmed
    ..This dual actin rearrangement may play a novel, important role in regulation of the neuronal morphology and motility during brain development. ..
  9. Ueda H. Peripheral mechanisms of neuropathic pain - involvement of lysophosphatidic acid receptor-mediated demyelination. Mol Pain. 2008;4:11 pubmed publisher
    ..These results lead to further hypotheses of physical communication between innocuous Abeta- and noxious C- or Adelta-fibers to influence the molecular mechanisms of allodynia. ..
  10. Bandoh K, Aoki J, Hosono H, Kobayashi S, Kobayashi T, Murakami Murofushi K, et al. Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. J Biol Chem. 1999;274:27776-85 pubmed
  11. Liliom K, Tsukahara T, Tsukahara R, Zelman Femiak M, Swiezewska E, Tigyi G. Farnesyl phosphates are endogenous ligands of lysophosphatidic acid receptors: inhibition of LPA GPCR and activation of PPARs. Biochim Biophys Acta. 2006;1761:1506-14 pubmed
    ..These results indicate new potential roles for the oligoprenyl phosphates as potential endogenous modulators of LPA targets and show that the polyisoprenoid chain is recognized by some LPA receptors. ..
  12. Tabata K, Baba K, Shiraishi A, Ito M, Fujita N. The orphan GPCR GPR87 was deorphanized and shown to be a lysophosphatidic acid receptor. Biochem Biophys Res Commun. 2007;363:861-6 pubmed
    ..These results suggest that the GPR87 is a LPA receptor which evolved from a common ancestor of P2Y receptors. ..
  13. Im D, Heise C, Harding M, George S, O Dowd B, Theodorescu D, et al. Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate. Mol Pharmacol. 2000;57:753-9 pubmed
    ..Edg-7 RNA was detected in extracts of several rat and human tissues including prostate. Together, our data indicate that Edg-7 is a third lysophosphatidic acid receptor that couples predominantly to G(q/11)alpha proteins. ..
  14. Deng W, Balazs L, Wang D, Van Middlesworth L, Tigyi G, Johnson L. Lysophosphatidic acid protects and rescues intestinal epithelial cells from radiation- and chemotherapy-induced apoptosis. Gastroenterology. 2002;123:206-16 pubmed
    ..3) LPA protects enterocytes against radiation-induced apoptosis. This study suggests that in patients undergoing cancer therapy, dietary LPA might have therapeutically useful antiapoptotic capacity in the intestinal epithelium. ..
  15. Sorensen S, Nicole O, Peavy R, Montoya L, Lee C, Murphy T, et al. Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. Mol Pharmacol. 2003;64:1199-209 pubmed
  16. Lee Z, Swaby R, Liang Y, Yu S, Liu S, Lu K, et al. Lysophosphatidic acid is a major regulator of growth-regulated oncogene alpha in ovarian cancer. Cancer Res. 2006;66:2740-8 pubmed
    ..The effect of serum on GROalpha production is also significantly decreased by siRNA inhibition of LPA(2) expression. These studies identify LPA as a primary regulator of GROalpha expression in ovarian cancer. ..
  17. Subramanian P, Karshovska E, Reinhard P, Megens R, Zhou Z, Akhtar S, et al. Lysophosphatidic acid receptors LPA1 and LPA3 promote CXCL12-mediated smooth muscle progenitor cell recruitment in neointima formation. Circ Res. 2010;107:96-105 pubmed publisher
    ..Moreover, POL5551 decreased the neointimal accumulation of CXCR4(+) SMCs. LPA(1) and LPA(3) promote neointima formation through activation of CXCL12-mediated mobilization and recruitment of SPCs. ..
  18. Hao F, Tan M, Xu X, Han J, Miller D, Tigyi G, et al. Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA(1), p42 and p38alpha. Biochim Biophys Acta. 2007;1771:883-92 pubmed
    ..The results of the present study suggest that LPA, the receptor LPA(1), ERK2 and p38alpha are important regulators for prostate cancer cell invasion and thus could play a significant role in the development of metastasis. ..
  19. Müller R, Berliner C, Leptin J, Pörtner D, Bialecki W, Kleuser B, et al. Expression of sphingosine-1-phosphate receptors and lysophosphatidic acid receptors on cultured and xenografted human colon, breast, melanoma, and lung tumor cells. Tumour Biol. 2010;31:341-9 pubmed publisher
    ..The latter was especially distinctive for small cell lung tumor cells. The S1P and LPA receptors are differentially expressed on tumor cell lines in vitro. Their expression is modulated upon xenografting into SCID mice in vivo...
  20. Tager A, LaCamera P, Shea B, Campanella G, Selman M, Zhao Z, et al. The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat Med. 2008;14:45-54 pubmed
    ..LPA1 therefore represents a new therapeutic target for diseases in which aberrant responses to injury contribute to fibrosis, such as idiopathic pulmonary fibrosis. ..
  21. Dottori M, Leung J, Turnley A, Pebay A. Lysophosphatidic acid inhibits neuronal differentiation of neural stem/progenitor cells derived from human embryonic stem cells. Stem Cells. 2008;26:1146-54 pubmed publisher
    ..As LPA concentrations increase during inflammation, the inhibition of neuronal differentiation by LPA might contribute to the low level of neurogenesis observed following neurotrauma. ..
  22. Hu Y, Tee M, Goetzl E, Auersperg N, Mills G, Ferrara N, et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J Natl Cancer Inst. 2001;93:762-8 pubmed
    ..However, this LPA response is not evident in normal ovarian surface epithelial cells. Our data suggest that Edg4, but not Edg2, plays a role in LPA stimulation of ovarian tumor growth. ..
  23. Malbon C. Beta-catenin, cancer, and G proteins: not just for frizzleds anymore. Sci STKE. 2005;2005:pe35 pubmed
    ..The ability of LPA to increase the cytoplasmic and nuclear accumulation of beta-catenin provides a new dimension of knowledge linking lipid mediators to the dysregulation of beta-catenin signaling in cancer. ..
  24. Yamada T, Sato K, Komachi M, Malchinkhuu E, Tobo M, Kimura T, et al. Lysophosphatidic acid (LPA) in malignant ascites stimulates motility of human pancreatic cancer cells through LPA1. J Biol Chem. 2004;279:6595-605 pubmed
    ..LPA receptor antagonists including Ki16425 are potential therapeutic drugs against the migration and invasion of cancer cells. ..
  25. Murph M, Tanaka T, Liu S, Mills G. Of spiders and crabs: the emergence of lysophospholipids and their metabolic pathways as targets for therapy in cancer. Clin Cancer Res. 2006;12:6598-602 pubmed
    ..Combined with the physiologic and pathophysiologic activities of LPA and S1P, these studies suggest the implementation of preclinical and clinical evaluation of LPA and S1P as therapeutic targets. ..
  26. Hecht J, Weiner J, Post S, Chun J. Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J Cell Biol. 1996;135:1071-83 pubmed
    ..Vzg-1 therefore provides a link between extracellular LPA and the activation of LPA-mediated signaling pathways through a single receptor and will allow new investigations into LPA signaling both in neural and nonneural systems. ..
  27. Li T, Alemayehu M, Aziziyeh A, Pape C, Pampillo M, Postovit L, et al. Beta-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells. Mol Cancer Res. 2009;7:1064-77 pubmed publisher
    ..Thus, our data show a novel role for beta-arrestin/Ral signaling in mediating LPA-induced breast cancer cell migration and invasion, two important processes in metastasis. ..
  28. Sato K, Malchinkhuu E, Muraki T, Ishikawa K, Hayashi K, Tosaka M, et al. Identification of autotaxin as a neurite retraction-inducing factor of PC12 cells in cerebrospinal fluid and its possible sources. J Neurochem. 2005;92:904-14 pubmed
    ..These results suggest that leptomeningeal cells may work as one of the sources for autotaxin, which may play a critical role in LPA production and thereby regulate axonal and neurite morphological change. ..
  29. Kotarsky K, Boketoft A, Bristulf J, Nilsson N, Norberg A, Hansson S, et al. Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes. J Pharmacol Exp Ther. 2006;318:619-28 pubmed
    ..Notably, GPR92 is highly expressed in the lymphocyte compartment of the gastrointestinal tract. It is the most abundant GPCR activated by LPA found in the small intestinal intraepithelial CD8+ cytotoxic T cells. ..
  30. Liu S, Umezu Goto M, Murph M, Lu Y, Liu W, Zhang F, et al. Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases. Cancer Cell. 2009;15:539-50 pubmed publisher
    ..Thus, ATX and LPA receptors can contribute to the initiation and progression of breast cancer. ..
  31. Yoshida A, Ueda H. Neurobiology of the Edg2 lysophosphatidic acid receptor. Jpn J Pharmacol. 2001;87:104-9 pubmed
    ..Here we focused their molecular basis of signaling through G proteins and in vivo roles of edg2 in such neurobiological events. ..
  32. McIntyre T, Pontsler A, Silva A, St Hilaire A, Xu Y, Hinshaw J, et al. Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist. Proc Natl Acad Sci U S A. 2003;100:131-6 pubmed
    ..Moreover, LPA produced by stimulated plasma platelets activates PPARgamma in nucleated cells. ..
  33. Wei Q, St Clair J, Fu T, Stratton P, Nieman L. Reduced expression of biomarkers associated with the implantation window in women with endometriosis. Fertil Steril. 2009;91:1686-91 pubmed publisher
    ..Because many of these markers are P dependent, these findings suggest the possibility of reduced endometrial P action in this population. ..
  34. He D, Su Y, Usatyuk P, Spannhake E, Kogut P, Solway J, et al. Lysophosphatidic acid enhances pulmonary epithelial barrier integrity and protects endotoxin-induced epithelial barrier disruption and lung injury. J Biol Chem. 2009;284:24123-32 pubmed publisher
    ..These data suggest a protective role of LPA in airway inflammation and remodeling. ..
  35. Zheng Y, Voice J, Kong Y, Goetzl E. Altered expression and functional profile of lysophosphatidic acid receptors in mitogen-activated human blood T lymphocytes. FASEB J. 2000;14:2387-9 pubmed
    ..Activation-induced alterations in the relative levels of Edg-2 and -4 Rs on CD4+ T cells thus reverse the effects of LPA on T cell receptor-stimulated generation of IL-2. ..
  36. Xu Y, Jiang G, Tsukahara R, Fujiwara Y, Tigyi G, Prestwich G. Phosphonothioate and fluoromethylene phosphonate analogues of cyclic phosphatidic acid: Novel antagonists of lysophosphatidic acid receptors. J Med Chem. 2006;49:5309-15 pubmed
    ..In contrast, the difluoromethylene phosphonate ccPA analogue was a weak LPAR agonist, while ccPA itself had neither agonist nor antagonist activity. ..
  37. Taghavi P, Verhoeven E, Jacobs J, Lambooij J, Stortelers C, Tanger E, et al. In vitro genetic screen identifies a cooperative role for LPA signaling and c-Myc in cell transformation. Oncogene. 2008;27:6806-16 pubmed publisher
    ..Our results reveal a direct role for LPA receptor signaling in cell transformation and tumorigenesis in conjunction with c-Myc and reduced p19Arf expression. ..
  38. Hasegawa Y, Murph M, Yu S, Tigyi G, Mills G. Lysophosphatidic acid (LPA)-induced vasodilator-stimulated phosphoprotein mediates lamellipodia formation to initiate motility in PC-3 prostate cancer cells. Mol Oncol. 2008;2:54-69 pubmed publisher
    ..Emerging drugs targeting the LPA pathway may be beneficial for the treatment of metastatic progression in prostate cancer. ..
  39. Hasegawa Y, Erickson J, Goddard G, Yu S, Liu S, Cheng K, et al. Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. J Biol Chem. 2003;278:11962-9 pubmed
    ..Thus OMPT offers a powerful probe for the dissection of LPA signaling events in complex mammalian systems. ..
  40. Yu S, Murph M, Lu Y, Liu S, Hall H, Liu J, et al. Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells. J Natl Cancer Inst. 2008;100:1630-42 pubmed publisher
    ..Expression of LPA2 or LPA3 during ovarian carcinogenesis contributes to ovarian cancer aggressiveness, suggesting that the targeting of LPA production and action may have potential for the treatment of ovarian cancer. ..
  41. Aoki J, Inoue A, Okudaira S. Two pathways for lysophosphatidic acid production. Biochim Biophys Acta. 2008;1781:513-8 pubmed publisher
    ..One PA-selective PLA1 called mPA-PLA1alpha/LIPH is specifically expressed in hair follicles, where it has a critical role in hair growth by producing LPA through a novel LPA receptor called P2Y5. ..
  42. Kortlever R, Brummelkamp T, van Meeteren L, Moolenaar W, Bernards R. Suppression of the p53-dependent replicative senescence response by lysophosphatidic acid signaling. Mol Cancer Res. 2008;6:1452-60 pubmed publisher
    ..Our results reveal a novel and unexpected link between LPA signaling and the p53 tumor-suppressive pathway. ..
  43. Inoue M, Yamaguchi A, Kawakami M, Chun J, Ueda H. Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain. Mol Pain. 2006;2:25 pubmed
    ..All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury. ..
  44. Ohta H, Sato K, Murata N, Damirin A, Malchinkhuu E, Kon J, et al. Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol. 2003;64:994-1005 pubmed
    ..In conclusion, Ki16425 selectively inhibits LPA receptor-mediated actions, especially through LPA1 and LPA3; therefore, it may be useful in evaluating the role of LPA and its receptor subtypes involved in biological actions. ..
  45. Valentine W, Fujiwara Y, Tsukahara R, Tigyi G. Lysophospholipid signaling: beyond the EDGs. Biochim Biophys Acta. 2008;1780:597-605 pubmed
    ..quot; Our observations raise caution about the lack of LPA responsiveness in these cells and underline the unprecedented complexity and redundancy of lysophospholipid-evoked cellular responses. ..
  46. Zhao Y, Usatyuk P, Cummings R, Saatian B, He D, Watkins T, et al. Lipid phosphate phosphatase-1 regulates lysophosphatidic acid-induced calcium release, NF-kappaB activation and interleukin-8 secretion in human bronchial epithelial cells. Biochem J. 2005;385:493-502 pubmed
    ..Our results identify LPP-1 as a key regulator of LPA signalling and IL-8 secretion in HBEpCs. Thus LPPs could represent potential targets in regulating leucocyte infiltration and airway inflammation. ..
  47. Gududuru V, Zeng K, Tsukahara R, Makarova N, Fujiwara Y, Pigg K, et al. Identification of Darmstoff analogs as selective agonists and antagonists of lysophosphatidic acid receptors. Bioorg Med Chem Lett. 2006;16:451-6 pubmed
    ..However, these compounds are weak inhibitors of autotaxin. The results indicate that Darmstoff analogs constitute a novel class of lysophosphatidic acid mimetics. ..
  48. Yamada T, Ohoka Y, Kogo M, Inagaki S. Physical and functional interactions of the lysophosphatidic acid receptors with PDZ domain-containing Rho guanine nucleotide exchange factors (RhoGEFs). J Biol Chem. 2005;280:19358-63 pubmed
    ..Taken together, these results indicate that formation of the LPA receptor/PDZ domain-containing RhoGEF complex plays a pivotal role in LPA-induced RhoA activation. ..
  49. Pebay A, Wong R, Pitson S, Wolvetang E, Peh G, Filipczyk A, et al. Essential roles of sphingosine-1-phosphate and platelet-derived growth factor in the maintenance of human embryonic stem cells. Stem Cells. 2005;23:1541-8 pubmed
    ..This study is the first demonstration of a role for lysophospholipid receptor signaling in the maintenance of stem cell pluri-potentiality. ..
  50. Noguchi K, Herr D, Mutoh T, Chun J. Lysophosphatidic acid (LPA) and its receptors. Curr Opin Pharmacol. 2009;9:15-23 pubmed publisher
    ..In addition, small molecule agonists and antagonists have been reported. Here we review recent data on the nervous system functions of LPA signaling, and summarize data on reported agonists and antagonists of LPA receptors. ..
  51. Rother E, Brandl R, Baker D, Goyal P, Gebhard H, Tigyi G, et al. Subtype-selective antagonists of lysophosphatidic Acid receptors inhibit platelet activation triggered by the lipid core of atherosclerotic plaques. Circulation. 2003;108:741-7 pubmed
    ..Antagonists of platelet LPA receptors might provide a new strategy to prevent thrombus formation in patients with cardiovascular diseases. ..
  52. Panchatcharam M, Miriyala S, Yang F, Rojas M, End C, Vallant C, et al. Lysophosphatidic acid receptors 1 and 2 play roles in regulation of vascular injury responses but not blood pressure. Circ Res. 2008;103:662-70 pubmed publisher
    ..These results identify a role for LPA1 and LPA2 in regulating SMC migratory responses in the context of vascular injury but suggest that additional LPA receptor subtypes are required for other LPA-mediated effects in the vasculature. ..
  53. Contos J, Ishii I, Fukushima N, Kingsbury M, Ye X, Kawamura S, et al. Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Mol Cell Biol. 2002;22:6921-9 pubmed
    ..Thus, although LPA(2) is not essential for normal mouse development, it does act redundantly with LPA(1) to mediate most LPA responses in fibroblasts. ..