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Showing LPAR2 — LPA2 is a alias.

LPAR2

Lysophosphatidic acid receptor 2 · UniProt Q9HBW0

Length
348 aa
Mass
38.7 kDa
Annotated
2026-06-10
91 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LPAR2 (LPA2/EDG4) is a lysophosphatidic acid-activated G protein-coupled receptor that transduces LPA signals through multiple heterotrimeric G proteins to control proliferation, survival, directional migration, barrier integrity, and tissue remodeling (PMID:12215548, PMID:11040035). It couples to Gi (Akt activation), Gq/PLC-beta (IP3/Ca2+, ERK), and G12/13/RhoA, and these outputs are organized by its C-terminal PDZ-binding motif, which nucleates a cytoskeleton-anchored macromolecular signaling complex (PMID:15728708, PMID:25542932). The receptor selectively binds the scaffold NHERF2 through the second PDZ domain to assemble a ternary LPA2/NHERF2/PLC-beta3 complex that potentiates PLC-beta, ERK, and Akt signaling and COX-2/IL-8 induction (PMID:15143197, PMID:15728708); the structural basis of this interaction lies in hydrogen bonds and hydrophobic contacts to the terminal LPA2 residues within the NHERF2 PDZ1 pocket (PMID:24613836). The competing scaffold MAGI-3 displaces NHERF2 and shifts coupling toward Galpha12, oppositely tuning PLC, NF-kappaB, JNK, and cell migration/invasion (PMID:21134377), while the adaptor TRIP6 recruits TRAF6 to sustain its E3 ligase activity by antagonizing A20/CYLD, thereby driving NF-kappaB and JNK signaling (PMID:27134758). Through Galpha12/13/RhoA the receptor phosphorylates ERM proteins to enable migration (PMID:29329782), and through Galphaq/Rho/Rho-kinase it transactivates alphavbeta6-integrin-dependent TGF-beta1 to elicit profibrotic cytokine secretion in epithelial and renal tubule cells (PMID:19147812, PMID:22885106). LPA2 also accelerates DNA repair after irradiation via ERK1/2 and PI3K/AKT in a manner dependent on its C-terminal cysteines (PMID:26027517), maintains endothelial and epithelial barrier integrity (PI3K-Akt/Erk and PLC-PKC-FAK pathways) (PMID:35920162, PMID:32654268, PMID:38026263), drives neuronal differentiation via ERK1/2 (PMID:35151977), and links LPA to canonical Wnt/beta-catenin signaling through PDZ-dependent interaction with Dishevelled (PMID:41418976).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Established that LPA2 is a functional LPA receptor coupling to multiple G proteins, defining its core signaling repertoire before any scaffold or pathway context was known.

    Evidence Retroviral expression in receptor-null B103 neuroblastoma cells with comparative signaling assays

    PMID:11040035

    Open questions at the time
    • Did not resolve which G protein drives which output
    • No scaffold or complex partners identified
  2. 2002 High

    Genetic knockout demonstrated that LPA2 contributes to LPA-induced PLC, Ca2+, adenylyl cyclase, proliferation, JNK, Akt, and stress fiber responses, acting redundantly with LPA1 in fibroblasts.

    Evidence lpa2-/- and lpa1-/-/lpa2-/- mice with embryonic fibroblast signaling assays

    PMID:12215548

    Open questions at the time
    • Redundancy obscured LPA2-specific functions
    • No molecular mechanism for selectivity among outputs
  3. 2004 High

    Identified the receptor-specific scaffold mechanism: LPA2 alone binds NHERF2 via its C-terminal PDZ motif to form a ternary complex with PLC-beta3 that amplifies signaling.

    Evidence Reciprocal Co-IP, PDZ motif mutagenesis, NHERF2 siRNA, IP/ERK assays

    PMID:15143197

    Open questions at the time
    • Atomic basis of binding specificity unresolved
    • Did not address competing scaffolds
  4. 2005 High

    Dissected the G protein origin of LPA2 outputs in cancer cells, showing Gi-dependent Akt and PLC-dependent ERK both require NHERF2 for full activation.

    Evidence Pertussis toxin, U-73122, NHERF2 siRNA, Co-IP in colon cancer cells

    PMID:15728708

    Open questions at the time
    • Mechanism linking NHERF2 to Gi coupling not defined
    • Functional consequence beyond IL-8 limited
  5. 2009 High

    Defined a Galphaq/RhoA/Rho-kinase axis through which LPA2 transactivates alphavbeta6-integrin-dependent TGF-beta, connecting the receptor to fibrosis-relevant signaling.

    Evidence siRNA, Galphaq/Rho/Rho-kinase inhibitors, TGF-beta activation assays in epithelial cells; pancreatic cancer G12/13/Rho migration study

    PMID:19129242 PMID:19147812

    Open questions at the time
    • Whether scaffold choice gates this axis not tested in this context
    • In vivo relevance not yet established at this stage
  6. 2010 High

    Revealed scaffold competition as a switch: MAGI-3 displaces NHERF2 to bias LPA2 toward Galpha12, oppositely regulating PLC, NF-kappaB, JNK, and invasion.

    Evidence Reciprocal Co-IP, MAGI-3 gain/loss-of-function, NF-kappaB reporter, migration/invasion assays in colon cancer

    PMID:21134377

    Open questions at the time
    • Determinants controlling scaffold ratio in vivo unknown
    • Structural basis of competition not resolved
  7. 2012 Medium

    Extended the antiapoptotic and profibrotic roles of LPA2, identifying TRIP6 as a third complex member for survival ERK signaling and confirming the Gq/alphavbeta6/TGF-beta fibrotic axis in vivo.

    Evidence LPA2-selective agonist GRI977143, Co-IP in reconstituted MEFs, caspase/DNA-fragmentation assays; proximal tubule cells with rat ischemia-reperfusion model

    PMID:22885106 PMID:22968304

    Open questions at the time
    • TRIP6 recruitment mechanism not yet defined
    • Causal contribution to organ fibrosis not isolated to LPA2
  8. 2014 High

    Provided structural and biophysical mechanism: a crystal structure of NHERF2 PDZ1 bound to the LPA2 C-terminus, plus single-particle tracking showing PDZ-anchored complex assembly creates a Ca2+ gradient for chemotactic sensing.

    Evidence X-ray crystallography of PDZ1-LPA2 peptide; single-particle tracking, PDZ mutagenesis, Ca2+ imaging, chemotaxis in fibroblasts; Xenopus neural crest N-cadherin internalization

    PMID:24613836 PMID:25002680 PMID:25542932

    Open questions at the time
    • Full-length receptor-scaffold structure unavailable
    • Cytoskeletal anchor identity not defined
  9. 2015 High

    Established LPA2 as a radioprotective DNA-repair factor whose function depends on its C-terminal cysteines, and characterized its distinctive desensitization behavior.

    Evidence Promoter mutagenesis, gamma-H2AX imaging, C-terminus mutagenesis, LPA2-reconstituted MEFs and KO mice; phosphorylation/internalization assays in C9 cells

    PMID:26027517 PMID:26473723

    Open questions at the time
    • Role of C-terminal cysteines mechanistically unexplained
    • Link between desensitization resistance and sustained signaling untested
  10. 2016 High

    Defined the molecular logic of LPA2-driven NF-kappaB/JNK signaling: TRIP6 recruits TRAF6 and protects its E3 ligase activity from deubiquitinases A20 and CYLD.

    Evidence Reciprocal Co-IP, TRIP6 shRNA/CRISPR, TRAF6-A20/CYLD binding assays, NF-kappaB/JNK reporters in ovarian cancer cells

    PMID:27134758

    Open questions at the time
    • Ubiquitin chain types on TRAF6 not characterized
    • How LPA2 conformation triggers TRIP6 recruitment unknown
  11. 2020 Medium

    Expanded physiological roles to immune and neural systems: LPA2 negatively regulates NF-kappaB in dendritic cells and dampens hippocampal network excitability.

    Evidence lpa2-/- mice, DC adoptive transfer, NF-kappaB reporter; electrophysiology, dentate gyrus RNAseq, pharmacological antagonism

    PMID:22427635 PMID:32468095

    Open questions at the time
    • Cell-autonomous neuronal mechanism not resolved
    • How the same receptor both activates and suppresses NF-kappaB in different cells unexplained
  12. 2022 High

    Demonstrated tissue-protective vascular and neurogenic functions through endothelial-specific genetics and pathway dissection.

    Evidence Endothelial-specific and global Lpar2 KO, adenoviral rescue, DBIBB activation, MI models; neural stem/progenitor differentiation with GRI977143 and ERK inhibitor

    PMID:35151977 PMID:35920162

    Open questions at the time
    • Endothelial scaffold partners not identified
    • Connection between barrier-protective and proliferative signaling branches unclear
  13. 2025 Medium

    Linked LPA2 to canonical Wnt signaling, showing PDZ-dependent interaction with Dishevelled 2/3 couples the receptor to beta-catenin signaling and migration.

    Evidence Co-IP of LPA2 with Dvl2/Dvl3, PDZminus mutant, beta-catenin reporter, migration/proliferation assays in colon cancer

    PMID:41418976

    Open questions at the time
    • Single-lab Co-IP without structural validation
    • How Dvl recruitment competes with NHERF2/MAGI-3 at the same motif unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single C-terminal PDZ motif arbitrates among competing scaffolds (NHERF2, MAGI-3, TRIP6, Dishevelled) to select distinct G protein outputs and physiological outcomes in a cell-type-specific manner remains unresolved.
  • No quantitative model of scaffold competition in vivo
  • No full-length receptor-scaffold complex structure
  • Cell-type determinants of scaffold availability uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0060089 molecular transducer activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 1
Partners
DVL2DVL3GPR55MAGI3NHERF2PLCB3TRAF6TRIP6
Complex memberships
LPA2/NHERF2/PLC-beta3 ternary complexLPA2/NHERF2/TRIP6 signaling complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 LPA2 (EDG4) knockout mice show loss of LPA-induced signaling responses (PLC activation, Ca2+ mobilization, adenylyl cyclase activation, proliferation, JNK activation, Akt activation, stress fiber formation) in embryonic fibroblasts, acting redundantly with LPA1; double knockout of lpa1/lpa2 nearly abolishes all these LPA-mediated responses in fibroblasts. Genetic knockout (lpa2-/- and lpa1-/-/lpa2-/- mice), embryonic fibroblast signaling assays Molecular and cellular biology High 12215548
2000 LPA2 (EDG4/LP(A2)) couples to multiple G proteins and mediates LPA-dependent inositol phosphate production, MAPK activation, arachidonic acid release, inhibition of cAMP accumulation, and cell rounding in neuronal cell lines; distinct from LPA3 which causes neurite elongation. Retrovirus expression system in B103 neuroblastoma cells (lacking endogenous LPA receptors), comparative signaling assays Molecular pharmacology High 11040035
2009 LPA induces alphavbeta6 integrin-mediated TGF-beta activation in human epithelial cells via LPA2 receptor signaling through Galpha(q), RhoA, and Rho kinase. Pharmacological inhibition (Galpha(q) inhibitor, RhoA/Rho kinase inhibitors), siRNA knockdown of LPA2, TGF-beta activation assays in epithelial cells The American journal of pathology High 19147812
2004 LPA2, but not other LPA receptor isoforms, specifically interacts with NHERF2 via the C-terminal PDZ domain-binding motif of LPA2 and the second PDZ domain of NHERF2; this interaction forms a ternary complex (LPA2/NHERF2/PLC-beta3) that potentiates LPA-induced PLC-beta activation, ERK activation, and COX-2 induction. Co-immunoprecipitation, PDZ domain-binding motif mutation, NHERF2 gene silencing (siRNA), stable expression, inositol phosphate and ERK assays Molecular and cellular biology High 15143197
2005 LPA2 activates Akt (via Gi/pertussis-toxin-sensitive pathway) and Erk1/2 (via PLCbeta/U-73122-sensitive pathway) in human colon cancer cells, and mediates LPA-induced IL-8 synthesis; LPA2 physically interacts with NHERF2 and this interaction is required for efficient Akt and Erk1/2 activation. Pertussis toxin inhibition, PLC inhibitor (U-73122), NHERF2 siRNA knockdown, co-immunoprecipitation in colon cancer cells American journal of physiology. Cell physiology High 15728708
2000 LPA-induced Ca2+ mobilization in SH-SY5Y neuroblastoma cells (which endogenously express EDG-4/LPA2) does not involve IP3 or ryanodine receptor pathways, but requires intracellular sphingosine 1-phosphate production via sphingosine kinase; LPA stimulates sphingosine 1-phosphate production and this lipid second messenger mobilizes intracellular Ca2+. 45Ca2+ release assays in permeabilized cells, sphingosine kinase inhibitor (dimethylsphingosine), confocal Ca2+ imaging, IP3 receptor down-regulation, [3H]sphingosine 1-phosphate measurement The Journal of biological chemistry Medium 10954727
2009 LPA2 receptor is coupled to the G12/13 protein/Rho-signaling pathway in pancreatic cancer cells, leading to RhoA activation and inhibition of EGF-induced cell migration and invasion; this is distinct from LPA1 which promotes migration. LPA2-specific siRNA knockdown, C3 toxin (RhoA inhibitor), LP-105 LPA2-selective agonist, pertussis toxin treatment, Transwell migration and Matrigel invasion assays Carcinogenesis Medium 19129242
2010 MAGI-3 competes with NHERF-2 for binding to LPA2 and to PLC-beta3; MAGI-3 increases LPA2 interaction with Galpha12 while NHERF-2 preferentially promotes interaction with Galphaq, thereby oppositely regulating LPA2-induced PLC activity, NF-kappaB activation, JNK activation, and cell migration/invasion. Co-immunoprecipitation, MAGI-3 overexpression and knockdown, NF-kappaB reporter assay, migration and invasion assays in colon cancer cells Gastroenterology High 21134377
2012 LPA2 receptor signals through Galphaqi to activate Rho/Rho-kinase and alphavbeta6 integrin-dependent TGF-beta1 transactivation in proximal tubule cells, leading to production and secretion of profibrotic cytokines PDGF-B and CTGF. LPA2 receptor assays in proximal tubule cells, pharmacological inhibitors (Rho kinase, alphavbeta6 integrin blocking antibody), TGF-beta activation assays, rat ischemia-reperfusion injury model The American journal of pathology High 22885106
2014 LPA2 mediates N-cadherin internalization in neural crest cells downstream of LPA, reducing cell-cell adhesion and triggering a partial mesenchymal phenotype that increases tissue fluidity and enables collective cell migration under physical constraints. Live imaging in Xenopus neural crest, LPA2 loss-of-function (morpholino), N-cadherin internalization assays, tissue rheology measurements The Journal of cell biology High 25002680
2012 LPA2-specific nonlipid agonist GRI977143 promotes assembly of a macromolecular signaling complex consisting of LPA2, NHERF2, and TRIP6 (thyroid receptor interacting protein 6), which mediates antiapoptotic ERK1/2 activation and reduces caspase activation, DNA fragmentation, and Bax translocation. Co-immunoprecipitation, LPA2-reconstituted MEF cells (LPA1&2 double-KO background), caspase assays, PARP cleavage, DNA fragmentation, ERK1/2 phosphorylation assays Molecular pharmacology Medium 22968304
2016 TRIP6 (an LPA2-interacting adaptor) recruits TRAF6 to the LPA2 receptor upon LPA stimulation and promotes LPA-induced JNK and NF-kappaB activation in a TRAF6-dependent manner; TRIP6 antagonizes binding of deubiquitinases A20 and CYLD to TRAF6, sustaining TRAF6 E3 ligase activity and augmenting NF-kappaB signaling. Co-immunoprecipitation, TRIP6 shRNA/Cas9 knockdown/knockout, TRAF6 binding assays with A20/CYLD, NF-kappaB and JNK reporter assays in ovarian cancer cells Cell discovery High 27134758
2014 A LPA gradient induces spatiotemporally restricted decrease in LPA2 mobility on fibroblasts, correlating with PDZ motif-mediated macromolecular complex assembly anchored to the cytoskeleton; this asymmetric complex generates a Ca2+ puff gradient that governs gradient sensing and directional migration. Disrupting the PDZ motif abolishes this gradient sensing. Single-particle tracking, PDZ motif mutagenesis, Ca2+ imaging, directional migration (chemotaxis) assays in fibroblasts The Journal of biological chemistry High 25542932
2014 Crystal structure of the NHERF2 PDZ1 domain in complex with the C-terminal LPA2 peptide sequence reveals that binding specificity is achieved through hydrogen bonds and hydrophobic contacts with the last four LPA2 residues; conformational flexibility in the ligand-binding pocket contributes to substrate recognition. X-ray crystallography of PDZ1–LPA2 C-terminal peptide complex Biochemical and biophysical research communications High 24613836
2015 Gamma-irradiation upregulates lpa2 expression in intestinal crypt cells via ATM kinase and NF-kappaB (mutation of NF-kappaB site in lpa2 promoter abolishes upregulation); LPA2 promotes DNA repair resolution (accelerated gamma-H2AX disappearance) via ERK1/2 and PI3K/AKT signaling; a C311A/C314A/L351A mutation in the LPA2 C-terminus abrogates this DNA repair function. Quantitative RT-PCR, promoter mutation analysis, gamma-H2AX immunofluorescence, pharmacological inhibition (CGK-733 ATM/ATR inhibitor, pertussis toxin), LPA2-reconstituted MEF cells, LPA2-KO mice, C-terminus mutagenesis Cellular signalling High 26027517
2011 LPA stimulates DRA (SLC26A3) gene transcription via the LPA2 receptor and PI3K/AKT pathway; LPA induces DRA promoter activity in a c-Fos-dependent manner, and overexpression of c-Fos (but not c-Jun) enhances DRA promoter activity. Receptor-specific pharmacology, PI3K/AKT inhibitors, DRA promoter-reporter assays, EMSA, mutational analysis of promoter, siRNA in Caco-2 cells American journal of physiology. Gastrointestinal and liver physiology Medium 22159277
2007 LPA2 mediates LPA-stimulated RhoA activation and cell migration in breast cancer cells (BT-20) with lower potency/efficacy than LPA1; LPA1 and LPA2 cooperate to promote LPA-stimulated chemotaxis, allowing response to a wider range of LPA concentrations. LPA2-specific siRNA knockdown, C3 exotransferase (RhoA inhibitor), LPA1 receptor overexpression, Ki16425 antagonist, Transwell chemotaxis assay American journal of physiology. Cell physiology Medium 17496233
2015 Phosphorylation of LPA2 requires higher agonist and PKC activator concentrations compared to LPA1 and LPA3; LPA2 internalization upon agonist or PKC stimulation is less intense than other subtypes; homologous desensitization of LPA2 is not affected by PKC inhibition or down-regulation, unlike LPA1/LPA3. Receptor phosphorylation assays, internalization assays, PKC inhibition/down-regulation, agonist desensitization in C9 cells expressing individual LPA receptors PloS one Medium 26473723
2018 LPA-induced migration of ovarian cancer cells (OVCAR-3) via LPA1 and LPA2 (but not LPA3) requires phosphorylation of ERM proteins (ezrin/radixin/moesin) at their C-termini through the Galpha12/13/RhoA pathway; dominant-negative ezrin (T567A) blocks LPA-induced migration. LPA1/LPA2 siRNA knockdown, Galpha12/13/RhoA pathway pharmacology, dominant-negative ezrin mutant overexpression, ERM phosphorylation assays, migration assays Cellular signalling Medium 29329782
2022 Endothelial LPA2 promotes angiogenesis and vascular homeostasis after myocardial infarction via PI3K-Akt/PLC-Raf1-Erk pathway (endothelial cell proliferation) and PKD1-CD36 signaling (tube formation); endothelial-specific Lpar2 KO phenocopies global KO with increased vascular leak, larger scar, and reduced vascular density. Global and endothelial-specific Lpar2 knockout mice, adenovirus-Lpar2 rescue, pharmacological LPA2 activation (DBIBB), MI and femoral artery ligation models, mechanistic pathway inhibitors Circulation research High 35920162
2017 LPA upregulates MMP-9 expression in macrophages through LPA2-dependent NF-kappaB p65 activation; knockdown of LPA2 attenuates LPA-induced MMP-9 expression and nuclear p65 translocation. AP-1 and PPARgamma inhibitors do not affect this pathway. LPA2 siRNA knockdown, NF-kappaB inhibitor (PDTC), NF-κB p65 siRNA, MMP-9 expression/activity assays, THP-1-derived macrophages and primary human macrophages Frontiers in physiology Medium 28496416
2025 LPA2 interacts with Wnt effectors Dvl2 and Dvl3 in colon cancer cells via the PDZ-interacting motif in the LPA2 C-terminus; the LPA2-PDZminus mutant (lacking PDZ interaction) inhibits cell migration but increases proliferation and impairs LPA2-mediated canonical Wnt signaling as well as Wnt-3a-induced beta-catenin signaling. Co-immunoprecipitation of LPA2 with Dvl2/Dvl3, LPA2-PDZminus mutant expression, beta-catenin reporter assay, ERK phosphorylation, migration and proliferation assays in colon cancer cells Cellular signalling Medium 41418976
2019 LPA2 mediates LPA-induced migration, invasion, EMT, and cytoskeletal remodeling of SGC-7901 gastric cancer cells; LPA2 physically interacts with Notch1 (shown by co-immunoprecipitation), and LPA stimulates Notch1/Hes1 expression and Akt phosphorylation. Co-immunoprecipitation (LPA2/Notch1), LPA2 and Notch1 siRNA knockdown, Transwell migration and invasion assays, EMT marker expression, immunofluorescent staining International journal of molecular medicine Low 31115486
2021 LPAR2 receptor activation protects colonic tight junctions from radiation injury via a Rho-kinase-dependent mechanism; Lpar2-/- mice show more severe TJ disruption after irradiation than wild-type; LPA2-specific agonist RP-1 alleviates radiation-induced barrier dysfunction and modulates cofilin activation and actin cytoskeleton remodeling. Lpar2-/- mice (total body irradiation), Caco-2/m-ICC12 cell monolayers, Rho-kinase inhibitor, barrier function (inulin permeability, TEER), TJ protein immunofluorescence, plasma LPS measurement FASEB journal Medium 32654268
2023 LPA-LPA2 signaling protects vascular endothelial barrier in septic acute lung injury via the PLC-PKC-FAK pathway; Lpar2 deficiency increases vascular permeability and worsens lung injury, while pharmacological LPA2 activation (DBIBB) reduces inflammation and preserves tight junction proteins (ZO-1, claudin-5) and VE-cadherin. Lpar2-/- mice (LPS sepsis model), DBIBB pharmacological activation, Evans blue dye permeability assay, TEER in MLMECs, Western blot for PLC/PKC/FAK pathway activation, immunofluorescence for TJ proteins Journal of inflammation research Medium 38026263
2020 LPA2 receptor mediates LPA-induced inhibition of neuronal network excitability in hippocampus; Lpar2-/- mice show decreased hippocampal network activity and increased LTP, with reduced transcription of neuronal activity markers (ARC, FOS, FOSB, NR4A2, NPAS4, EGR2) in dentate gyrus; pharmacological LPA2 blockade recapitulates this phenotype. Lpar2-/- mice, electrophysiology (LTP, network activity), RNAseq of dentate gyrus, pharmacological LPA2 antagonism, behavioral cognitive assays Cellular and molecular life sciences Medium 32468095
2020 LPA2 in dendritic cells negatively regulates NF-kappaB-driven gene transcription; lpa2-/- dendritic cells are hyperactive and less susceptible to LPA-mediated inhibition; adoptive transfer of lpa2-/- DCs induces more lung inflammation than WT DCs. Lpa2-/- mice, DC adoptive transfer, NF-kappaB reporter (transient transfection), allergen challenge models (OVA and Schistosoma egg), BAL cytokine measurement Journal of immunology Medium 22427635
2022 LPA2 promotes neuronal differentiation of neural stem/progenitor cells via ERK1/2 signaling, and promotes neurite elongation and branching; LPA2 activation with GRI977143 induces neuronal differentiation that is blocked by ERK1/2 inhibitor FR180204. LPA2-selective agonist (GRI977143), ERK1/2 inhibitor (FR180204), primary neural stem/progenitor cell culture, neuronal differentiation assays, neurite morphology analysis Biochemical and biophysical research communications Medium 35151977
2021 LPA2 and GPR55 physically interact in live cells (BRET analysis); co-activation of both receptors synergistically reduces intracellular cAMP and promotes cell proliferation beyond either receptor alone; co-activation facilitates co-internalization of both receptors. Bioluminescence resonance energy transfer (BRET) in live cells, cAMP assay, proliferation assay, receptor co-internalization imaging FEBS letters Medium 33959968
2022 LPA induces beta-catenin nuclear localization and transcriptional activity, GSK-3beta phosphorylation, Axin2 downregulation, and increased ATP production via both oxidative phosphorylation and glycolysis in gastric cancer cells, all through the LPAR2 receptor; LPAR2 antagonism or knockdown abrogates these effects. LPAR2 antagonist, LPAR2 siRNA knockdown, beta-catenin reporter and localization assays, Seahorse metabolic assay, Western blot for GSK-3beta/Axin2 Biomolecules Medium 36551233

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 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). Molecular and cellular biology 262 12215548
2009 Lysophosphatidic acid induces alphavbeta6 integrin-mediated TGF-beta activation via the LPA2 receptor and the small G protein G alpha(q). The American journal of pathology 178 19147812
2000 Functional comparisons of the lysophosphatidic acid receptors, LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7 in neuronal cell lines using a retrovirus expression system. Molecular pharmacology 164 11040035
2003 The maize low-phytic acid mutant lpa2 is caused by mutation in an inositol phosphate kinase gene. Plant physiology 125 12586875
2009 The absence of LPA2 attenuates tumor formation in an experimental model of colitis-associated cancer. Gastroenterology 110 19328876
2014 In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity. The Journal of cell biology 108 25002680
2005 LPA2 receptor mediates mitogenic signals in human colon cancer cells. American journal of physiology. Cell physiology 96 15728708
2012 Lysophosphatidic acid increases proximal tubule cell secretion of profibrotic cytokines PDGF-B and CTGF through LPA2- and Gαq-mediated Rho and αvβ6 integrin-dependent activation of TGF-β. The American journal of pathology 85 22885106
2001 Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. International journal of cancer 78 11291053
2007 LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. American journal of physiology. Cell physiology 77 17496233
2004 NHERF2 specifically interacts with LPA2 receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-beta3 activation. Molecular and cellular biology 76 15143197
2000 Lysophosphatidic acid-induced Ca2+ mobilization requires intracellular sphingosine 1-phosphate production. Potential involvement of endogenous EDG-4 receptors. The Journal of biological chemistry 65 10954727
2000 Genomic characterization of the lysophosphatidic acid receptor gene, lp(A2)/Edg4, and identification of a frameshift mutation in a previously characterized cDNA. Genomics 59 10729222
2012 Virtual screening for LPA2-specific agonists identifies a nonlipid compound with antiapoptotic actions. Molecular pharmacology 57 22968304
2009 LPA1 receptors mediate stimulation, whereas LPA2 receptors mediate inhibition, of migration of pancreatic cancer cells in response to lysophosphatidic acid and malignant ascites. Carcinogenesis 56 19129242
2010 MAGI-3 competes with NHERF-2 to negatively regulate LPA2 receptor signaling in colon cancer cells. Gastroenterology 53 21134377
2022 LPA2 Contributes to Vascular Endothelium Homeostasis and Cardiac Remodeling After Myocardial Infarction. Circulation research 51 35920162
2009 Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma. Respiratory research 51 19930563
2014 Regulation of T cell motility in vitro and in vivo by LPA and LPA2. PloS one 47 25003200
2012 Lpa2 is a negative regulator of both dendritic cell activation and murine models of allergic lung inflammation. Journal of immunology (Baltimore, Md. : 1950) 47 22427635
2004 Induction of protein growth factor systems in the ovaries of transgenic mice overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor (LPA2). Oncogene 47 14712217
2015 The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair. Cellular signalling 44 26027517
2019 LPA1 , LPA2 , LPA4 , and LPA6 receptor expression during mouse brain development. Developmental dynamics : an official publication of the American Association of Anatomists 43 30847983
2018 LPA-induced migration of ovarian cancer cells requires activation of ERM proteins via LPA1 and LPA2. Cellular signalling 38 29329782
2015 Combined mitigation of the gastrointestinal and hematopoietic acute radiation syndromes by an LPA2 receptor-specific nonlipid agonist. Chemistry & biology 35 25619933
2008 Discovery of potent LPA2 (EDG4) antagonists as potential anticancer agents. Bioorganic & medicinal chemistry letters 34 18178086
2016 Higher LPA2 and LPA6 mRNA Levels in Hepatocellular Carcinoma Are Associated with Poorer Differentiation, Microvascular Invasion and Earlier Recurrence with Higher Serum Autotaxin Levels. PloS one 33 27583415
2009 Lysophosphatidic acid-induced arterial wall remodeling: requirement of PPARgamma but not LPA1 or LPA2 GPCR. Cellular signalling 32 19709640
2013 Mitigation of radiation injury by selective stimulation of the LPA(2) receptor. Biochimica et biophysica acta 31 23127512
2019 Lysophosphatidic acid induces the migration and invasion of SGC-7901 gastric cancer cells through the LPA2 and Notch signaling pathways. International journal of molecular medicine 30 31115486
2017 Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in Macrophages. Frontiers in physiology 29 28496416
2020 Effects of lysophosphatidic acid (LPA) receptor-2 (LPA2) and LPA3 on the regulation of chemoresistance to anticancer drug in lung cancer cells. Cellular signalling 28 32006610
2011 LPA stimulates intestinal DRA gene transcription via LPA2 receptor, PI3K/AKT, and c-Fos-dependent pathway. American journal of physiology. Gastrointestinal and liver physiology 25 22159277
2008 Regulation of the LPA2 receptor signaling through the carboxyl-terminal tail-mediated protein-protein interactions. Biochimica et biophysica acta 25 18501721
2015 Phosphorylation and Internalization of Lysophosphatidic Acid Receptors LPA1, LPA2, and LPA3. PloS one 22 26473723
2020 Prevention of age-associated neuronal hyperexcitability with improved learning and attention upon knockout or antagonism of LPAR2. Cellular and molecular life sciences : CMLS 21 32468095
2020 Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway. Frontiers in molecular neuroscience 20 32116549
2018 The LPA2 receptor agonist Radioprotectin-1 spares Lgr5-positive intestinal stem cells from radiation injury in murine enteroids. Cellular signalling 20 30063964
2016 TRIP6 antagonizes the recruitment of A20 and CYLD to TRAF6 to promote the LPA2 receptor-mediated TRAF6 activation. Cell discovery 18 27134758
2008 Lysophosphatidic acid stimulates the proliferation and motility of malignant pleural mesothelioma cells through lysophosphatidic acid receptors, LPA1 and LPA2. Cancer science 18 18754873
2023 Combined inhibition of EZH2 and the autotaxin-LPA-LPA2 axis exerts synergistic antitumor effects on colon cancer cells. Cancer letters 17 37230222
2020 LPAR2 receptor activation attenuates radiation-induced disruption of apical junctional complexes and mucosal barrier dysfunction in mouse colon. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 32654268
2005 Differential effects of lysolipids on steroid synthesis in cells expressing endogenous LPA2 receptor. Journal of lipid research 17 15716590
2017 Enhanced cellular functions through induction of LPA2 by cisplatin in fibrosarcoma HT1080 cells. Molecular and cellular biochemistry 16 28205098
2022 Efficacy Comparison of LPA2 Antagonist H2L5186303 and Agonist GRI977143 on Ovalbumin-Induced Allergic Asthma in BALB/c Mice. International journal of molecular sciences 15 36077141
2021 Dual Role of Lysophosphatidic Acid Receptor 2 (LPA2) in Amyotrophic Lateral Sclerosis. Frontiers in cellular neuroscience 15 33841099
2021 LPA2 protein is involved in photosystem II assembly in Chlamydomonas reinhardtii. The Plant journal : for cell and molecular biology 15 34218480
2020 Autotaxin stimulates LPA2 receptor in macrophages and exacerbates dextran sulfate sodium-induced acute colitis. Journal of molecular medicine (Berlin, Germany) 15 33128578
2021 Gintonin regulates inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and carrageenan/kaolin-induced arthritis in rats through LPAR2. Journal of ginseng research 14 34803427
2022 Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model. Molecular therapy oncolytics 13 36090480
2021 Proximal tubule LPA1 and LPA2 receptors use divergent signaling pathways to additively increase profibrotic cytokine secretion. American journal of physiology. Renal physiology 13 33427061
2021 Phosphatidic Acid Stimulates Myoblast Proliferation through Interaction with LPA1 and LPA2 Receptors. International journal of molecular sciences 13 33535610
2014 Design and synthesis of sulfamoyl benzoic acid analogues with subnanomolar agonist activity specific to the LPA2 receptor. Journal of medicinal chemistry 13 25100502
2018 Lysophosphatidic acid receptor-2 (LPA2) and LPA5 regulate cellular functions during tumor progression in fibrosarcoma HT1080 cells. Biochemical and biophysical research communications 12 30093116
2017 CFTR-NHERF2-LPA₂ Complex in the Airway and Gut Epithelia. International journal of molecular sciences 12 28869532
2014 Structural insights into PDZ-mediated interaction of NHERF2 and LPA(2), a cellular event implicated in CFTR channel regulation. Biochemical and biophysical research communications 11 24613836
1996 Direct and modulatory effects of FMRFamide, SKPYMRFamide and acety1-SKPYMRFamide on LPa2, LPa3, and RPa3 identified neurons of Helix lucorum. Regulatory peptides 11 8988517
2022 Compensatory Upregulation of LPA2 and Activation of the PI3K-Akt Pathway Prevent LPA5-Dependent Loss of Intestinal Epithelial Cells in Intestinal Organoids. Cells 10 35883686
2020 Cooperation of G12/13 and Gi proteins via lysophosphatidic acid receptor-2 (LPA2) signaling enhances cancer cell survival to cisplatin. Biochemical and biophysical research communications 10 32883524
2007 Alkoxymethylenephosphonate analogues of (Lyso) phosphatidic acid stimulate signaling networks coupled to the LPA2 receptor. ChemMedChem 10 17952880
2022 Alteration of Cellular Energy Metabolism through LPAR2-Axin2 Axis in Gastric Cancer. Biomolecules 9 36551233
2020 Development and validation of breeder-friendly gene-based markers for lpa1-1 and lpa2-1 genes conferring low phytic acid in maize kernel. 3 Biotech 9 32123645
2020 Different effects of lysophosphatidic acid receptor-2 (LPA2) and LPA5 on the regulation of chemoresistance in colon cancer cells. Journal of receptor and signal transduction research 9 32672083
2018 LPAR2 and LPAR4 are the Main Receptors Responsible for LPA Actions in Ovarian Endometriotic Cysts. Reproductive sciences (Thousand Oaks, Calif.) 9 29621954
2022 Novel Antagonist of the Type 2 Lysophosphatidic Acid Receptor (LPA2), UCM-14216, Ameliorates Spinal Cord Injury in Mice. Journal of medicinal chemistry 8 35948083
2014 Asymmetrical macromolecular complex formation of lysophosphatidic acid receptor 2 (LPA2) mediates gradient sensing in fibroblasts. The Journal of biological chemistry 8 25542932
2022 LPA2 promotes neuronal differentiation and neurite formation in neocortical development. Biochemical and biophysical research communications 7 35151977
2020 Roles of endothelial cells in the regulation of cell motility via lysophosphatidic acid receptor-2 (LPA2) and LPA3 in osteosarcoma cells. Experimental and molecular pathology 7 33347862
2023 Roles of lysophosphatidic acid (LPA) receptor-2 (LPA2) in the regulation of cellular responses induced by X-ray irradiation and hydrogen peroxide in pancreatic cancer cells. International journal of radiation biology 6 37523658
2021 Interplay between LPA2 and LPA3 in LPA-mediated phosphatidylserine cell surface exposure and extracellular vesicles release by erythrocytes. Biochemical pharmacology 6 34216604
2021 BRET analysis reveals interaction between the lysophosphatidic acid receptor LPA2 and the lysophosphatidylinositol receptor GPR55 in live cells. FEBS letters 5 33959968
2016 Transgenic Expression of Human Lysophosphatidic Acid Receptor LPA2 in Mouse Intestinal Epithelial Cells Induces Intestinal Dysplasia. PloS one 5 27124742
2015 NT-3 protein levels are enhanced in the hippocampus of PRG1-deficient mice but remain unchanged in PRG1/LPA2 double mutants. Neuroscience letters 5 26687273
2002 Native and recombinant human Edg4 receptor-mediated Ca(2+) signalling. Assay and drug development technologies 5 15090154
2023 A dual role of lysophosphatidic acid type 2 receptor (LPAR2) in nonsteroidal anti-inflammatory drug-induced mouse enteropathy. Acta pharmacologica Sinica 4 37816857
2022 LPAR2-mediated action promotes human renal cell carcinoma via MAPK/NF-κB signaling to regulate cytokine network. Journal of cancer research and clinical oncology 4 35857125
2007 [Expression and significance of Edg4 and Edg7 in the placentas of patients with hypertensive disorder complicating pregnancy]. Zhonghua fu chan ke za zhi 4 17697599
2023 Differential targeting of lysophosphatidic acid LPA1, LPA2, and LPA3 receptor signalling by tricyclic and tetracyclic antidepressants. European journal of pharmacology 3 37758013
2023 LPA2 Alleviates Septic Acute Lung Injury via Protective Endothelial Barrier Function Through Activation of PLC-PKC-FAK. Journal of inflammation research 3 38026263
2008 Full-length coding sequences, polymorphism and chromosomal localizations of the porcine EDG4 and EDG7 genes. Molecular biology reports 3 18379896
2022 Estrogen-increased SGK1 Promotes Endometrial Stromal Cell Invasion in Adenomyosis by Regulating with LPAR2. Reproductive sciences (Thousand Oaks, Calif.) 2 35799024
2025 Spatiotemporal expression of lpa1 and lpa2 genes showed low phytate accumulation in maize foliage and seeds during early developmental stages. Plant physiology and biochemistry : PPB 1 41138698
2025 Inhibition of autotaxin sensitizes colon cancer to radiation by suppressing LPAR2-AKT survival signaling. BMC gastroenterology 1 41454227
2024 A mutation in LPAR2 activates the miR-939-5p-LPAR2-PI3K/AKT axis to regulate the proliferation and apoptosis of granulosa cells in sheep. Theriogenology 1 38368704
2024 Circ_0007611 modulates the miR-34c-5p/LPAR2 cascade to suppress proliferation and enhance apoptosis of HTR-8/SVneo cells. Placenta 1 38986295
2024 Lysophosphatidic Acid Receptors LPAR5 and LPAR2 Inversely Control Hydroxychloroquine-Evoked Itch and Scratching in Mice. International journal of molecular sciences 1 39125747
2026 Insights into the binding mechanism and structural requirements of LPAR2 antagonists as antifibrotic agents based on homology modeling, molecular docking, prediction of membrane permeability and 3D QSAR. Journal of computer-aided molecular design 0 42080966
2025 The LPA2 receptor PDZ domain affects canonical Wnt signaling in colon cancer cells. Cellular signalling 0 41418976
2025 Engineering Native-like GPCR Antigens Enables Discovery of an LPA2-Blocking Antibody for Ovarian Cancer. ACS synthetic biology 0 41476039
2024 Regulation of cellular responses to X-ray irradiation through the activation of lysophosphatidic acid (LPA) receptor-3 (LPA3) and LPA2 in osteosarcoma cells. Pathology, research and practice 0 38615508
2007 [Vector construction and silencing effect of Edg4 gene targeted small interfering RNA in ovarian cancer cell line]. Zhonghua fu chan ke za zhi 0 18307905

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