Affinage

GPR34

Probable G-protein coupled receptor 34 · UniProt Q9UPC5

Length
381 aa
Mass
43.9 kDa
Annotated
2026-04-28
46 papers in source corpus 24 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPR34 is a Gi/o-coupled G protein-coupled receptor for lysophosphatidylserine (LysoPS) that transduces lipid-damage signals into immune cell activation, phagocytosis, efferocytosis, and inflammatory cytokine production across microglia, macrophages, dendritic cells, and innate lymphoid cells. The receptor recognizes 2-acyl LysoPS through a laterally open orthosteric pocket — structurally defined by cryo-EM — in which the serine head group engages a polar cavity in TM3/TM6/TM7 and the acyl chain enters via a hydrophobic groove between TM3–5, activating downstream PI3K-AKT, ERK, and NF-κB/CRE/AP1 signaling cascades (PMID:22343749, PMID:37733739, PMID:38326347, PMID:22966169, PMID:34107271). GPR34 deficiency impairs microglial phagocytosis, dendritic cell survival, and ILC3-mediated tissue repair, whereas gain-of-function C-terminal truncation mutations — recurrent in MALT lymphoma — abolish β-arrestin-mediated desensitization and drive constitutive pro-survival signaling (PMID:25142016, PMID:26851221, PMID:34086889, PMID:29674500). In the tumor microenvironment, LysoPS–GPR34 signaling on ILC1s suppresses antitumor immunity while on macrophages it promotes efferocytosis-coupled MHC-I degradation and CD8+ T cell exhaustion (PMID:39358444, PMID:42045172).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2005 Medium

    Before ligand identity was known, the basic gene structure was resolved: GPR34 uses multiple conserved in-frame AUG translation initiation sites and undergoes alternative splicing that truncates the N-terminus, establishing post-transcriptional regulation of receptor isoforms.

    Evidence Combinatory mutagenesis and reporter constructs across vertebrate orthologs

    PMID:16338117

    Open questions at the time
    • Functional consequence of different N-terminal isoforms unknown
    • No ligand identified at this stage
  2. 2010 High

    GPR34 knockout mice revealed that the receptor is essential for normal immune cell function — regulating macrophage accumulation, delayed-type hypersensitivity, and pathogen clearance — but its endogenous ligand remained unidentified.

    Evidence Global GPR34 KO mice challenged with immunization, DTH, and Cryptococcus neoformans pulmonary infection

    PMID:21097509

    Open questions at the time
    • Ligand identity not yet established
    • Cell-type-specific contributions unresolved
  3. 2012 High

    Two simultaneous advances established that GPR34 is a receptor for 2-acyl lysophosphatidylserine (LysoPS) and a Gi/o-coupled GPCR that activates ERK, PKC, CREB, CRE, AP1, and NF-κB, linking ligand identity to intracellular signaling and revealing deregulation in MALT lymphoma via IGH translocation.

    Evidence LysoPS calcium/migration/AP-TGFα assays with enzymatic PS-PLA1 ligand generation; overexpression-driven phosphorylation and reporter assays in lymphoma/HeLa cells; FISH identification of t(X;14) translocation

    PMID:22343749 PMID:22966169

    Open questions at the time
    • Structural basis of LysoPS recognition unknown
    • In vivo ligand-receptor axis not validated in immune physiology
  4. 2014 High

    GPR34 was shown to be essential for microglial phagocytosis in the CNS — its loss altered microglial morphology and transcriptional programs — and to drive LysoPS-dependent cancer cell migration via PI3K/Akt, extending its functional scope beyond classical immune cells.

    Evidence GPR34 KO mouse retinal/cortical microglia phagocytosis assays with RNA-seq; siRNA knockdown in colorectal cancer cells with chemotaxis assay and wortmannin inhibition

    PMID:25142016 PMID:25275042

    Open questions at the time
    • LysoPS source for microglial GPR34 activation unidentified
    • Single colorectal cancer study with siRNA only
  5. 2016 High

    Molecular determinants of GPR34 biogenesis were defined: a tri-basic motif in the first intracellular loop controls TM1 topology, and its disruption arrests trafficking in the Golgi. Separately, GPR34 was shown to promote dendritic cell survival by suppressing caspase-3/7-mediated apoptosis.

    Evidence Systematic site-directed mutagenesis with conformational epitope and trafficking readouts; GPR34 KO DC caspase-3/7 and apoptosis assays

    PMID:26851221 PMID:27086875

    Open questions at the time
    • Broader relevance of tri-basic motif to other GPCRs not explored
    • DC survival mechanism downstream of GPR34 not fully characterized
  6. 2018 Medium

    Sequencing of MALT lymphoma identified recurrent C-terminal truncation mutations in GPR34 that eliminate the β-arrestin desensitization motif, providing a genetic mechanism for gain-of-function signaling in lymphomagenesis.

    Evidence Whole exome sequencing of 21 MALT lymphoma cases with structural annotation of truncation sites

    PMID:29674500

    Open questions at the time
    • Functional validation of truncation mutants not yet performed at this stage
    • β-arrestin binding loss inferred from motif deletion, not directly demonstrated
  7. 2019 High

    The LysoPS–GPR34 axis was established as a driver of microglial neuroinflammation and neuropathic pain: endogenous LysoPS accumulates in the spinal dorsal horn after nerve injury and activates GPR34 on microglia to induce pro-inflammatory cytokines.

    Evidence GPR34 KO mice with attenuated pain behavior; LC-MS/MS quantification of dorsal horn LysoPS; intrathecal GPR34 antagonist

    PMID:30975169

    Open questions at the time
    • Source cell type generating LysoPS after nerve injury not identified
    • Downstream effectors beyond cytokines not characterized
  8. 2021 High

    Cell-type-specific deletion revealed that GPR34 on ILC3s senses LysoPS from apoptotic neutrophils to activate PI3K-AKT/ERK signaling and produce IL-22 for intestinal tissue repair, establishing a damage-sensing–tissue-repair circuit.

    Evidence ILC3-specific Gpr34 conditional KO mice; metabolomic identification of LysoPS; co-culture with apoptotic neutrophils; colitis and skin injury models

    PMID:34107271

    Open questions at the time
    • Whether other LysoPS receptors contribute to ILC3 activation unclear
    • Mechanism linking PI3K-AKT to IL-22 transcription not defined
  9. 2022 High

    The MALT lymphoma GPR34 Q340X truncation mutant was functionally validated as a gain-of-function allele: it showed delayed internalization, constitutive CRE/NF-κB/AP1 activation, enhanced apoptosis resistance, and transforming potential, and its expressing cells generated autocrine LysoPS via secreted phospholipase activity.

    Evidence Isogenic Flp-In TRex293 cells with single-copy GPR34 WT vs. Q340X; internalization, reporter, apoptosis, and transformation assays; phospholipase activity measurement

    PMID:34086889

    Open questions at the time
    • In vivo lymphomagenesis not tested with mutant allele
    • Identity of secreted phospholipase not determined
  10. 2023 High

    Three independent cryo-EM structures of the GPR34–Gi–LysoPS complex resolved the atomic mechanism of lipid recognition: a laterally open binding pocket permits membrane entry of the acyl chain while a polar cavity in TM3/6/7 coordinates the serine head group, and a selective antagonist (YL-365) was co-crystallized in the orthosteric site.

    Evidence Cryo-EM of active LysoPS-Gi and inactive YL-365-bound complexes from three independent laboratories

    PMID:37733739 PMID:38048360 PMID:38326347

    Open questions at the time
    • No structure with 2-arachidonoyl LysoPS or other endogenous acyl variants
    • Activation mechanism at the G protein interface not fully compared across LysoPS receptor family
  11. 2023 Medium

    GPR34 knockdown in microglia and APP/PS1 mice reduced amyloid-β-induced neuroinflammation via ERK/NF-κB, and epistasis with ERK inhibition placed GPR34 upstream of ERK in microglial inflammatory signaling.

    Evidence GPR34 KD/OE in BV-2 cells, APP/PS1 mice, ERK inhibitor FR180204 epistasis

    PMID:37557947

    Open questions at the time
    • BV-2 is an immortalized cell line with caveats for primary microglia biology
    • Direct interaction between GPR34 and ERK not demonstrated
  12. 2024 High

    Multiple studies extended GPR34's immune roles: on ILC1s it acts as a metabolic immune checkpoint suppressing antitumor immunity; in macrophages it promotes efferocytosis-coupled MHC-I degradation driving CD8+ T cell exhaustion; in retinal microglia it activates a PI3K-AKT-NINJ1 axis promoting neovascularization; and LysoPS from myelin debris drives GPR34-dependent neuroinflammation in MS and stroke models. Stromally expressed PLA1A was identified as the relevant LysoPS-generating enzyme for peritoneal immune cell maintenance via GPR34.

    Evidence ILC1-specific Gpr34 KO and tumor Abhd16a KO; macrophage-specific Gpr34 KO with MHC-I assays; retinal microglia GPR34 signaling assays; EAE/stroke models; GPR34 knock-in B cells with PLA1A-deficient mice

    PMID:39030423 PMID:39358444 PMID:39412501 PMID:39468551 PMID:42045172

    Open questions at the time
    • Relative contribution of PLA1A vs. ABHD16A as LysoPS source varies by tissue — systematic comparison lacking
    • GPR34 signaling specificity across different immune cell types not fully resolved
  13. 2025 High

    GPR34 was shown to promote efferocytosis and cross-presentation in cDC1s (PLA1A-dependent), to be stabilized by USP8 deubiquitination, and agonist M1 enhanced microglial phagocytosis of Aβ fibrils in a TREM2-dependent and cAMP-reducing manner, establishing a therapeutic strategy for amyloid clearance.

    Evidence GPR34 KO/OE with OT-I cross-presentation assays and PLA1A/ABHD16A KO comparison; USP8 co-IP and GPR34 KO ferroptosis rescue; M1 agonist flow cytometry phagocytosis with cAMP measurement, Gpr34 KD, and in vivo APP-KI mice

    PMID:40862294 PMID:41212150 PMID:41261421

    Open questions at the time
    • USP8–GPR34 interaction validated by co-IP in one study only
    • TREM2–GPR34 epistasis mechanism not defined at molecular level
    • In vivo therapeutic efficacy of GPR34 agonism for Alzheimer's disease not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the molecular basis for GPR34 signaling divergence across immune cell types (pro-inflammatory in microglia vs. immunosuppressive in ILC1s), the complete catalog of physiological LysoPS sources and acyl-chain preferences in vivo, and whether GPR34-targeted therapeutics can achieve cell-type-selective modulation.
  • No cell-type-resolved signaling atlas for GPR34
  • No clinical trials or pharmacokinetic data for GPR34 agonists or antagonists
  • Structural basis for selectivity among LysoPS receptor family members (GPR34, GPR174, P2Y10) incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0008289 lipid binding 3
Localization
GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3
Partners
ABHD16AGNAI1PLA1ATREM2USP8

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 GPR34 is a cellular receptor for lysophosphatidylserine (LysoPS), particularly with a fatty acid at the sn-2 position. LysoPS elevated intracellular Ca2+ in HEK293 cells expressing GPR34 and a Gαq/i1 chimera, stimulated AP-TGFα release, and induced migration of CHO-K1 cells expressing GPR34. The serine head group of LysoPS was strictly required for receptor activation. Recombinant PS-PLA1 (which produces 2-acyl-LysoPS) but not catalytically inactive PS-PLA1 stimulated GPR34-dependent responses, confirming enzymatic generation of the ligand. Calcium assay, AP-TGFα release assay, chemotaxis assay, enzymatic ligand generation with wild-type vs. inactive PS-PLA1 mutant in HEK293 and CHO-K1 cells expressing GPR34 Journal of biochemistry High 22343749
2023 Cryo-EM structure of GPR34 bound to LysoPS(18:1) and Gi protein revealed that the negatively charged serine head group of LysoPS occupies a polar cavity formed by TM3, TM6, and TM7, while the hydrophobic tail resides in a lateral open hydrophobic groove formed by TM3-5, indicating lateral membrane entry of the lipid agonist. A selective antagonist (YL-365) was identified that competitively occupies a portion of the orthosteric binding pocket and induces allosteric changes in the receptor. Cryo-EM structure determination of active (LysoPS-Gi) and inactive (YL-365-bound) GPR34 complexes; virtual screening; functional assays; neuropathic pain model Proceedings of the National Academy of Sciences of the United States of America High 37733739
2024 Cryo-EM structures of human GPR34-Gi complex bound with LysoPS analogue S3E-LysoPS or M1 showed a laterally open ligand-binding pocket allowing membrane entry of lipidic agonists. The serine amine and carboxylate groups are recognized by a charged residue cluster, and the acyl chain fits into an L-shaped hydrophobic pocket in the TM4-5 gap. Molecular dynamics simulations supported 2-acyl LysoPS as the physiological ligand. Cryo-EM structure determination, molecular dynamics simulations, functional validation with LysoPS analogues Nature communications High 38326347
2023 Cryo-EM structures of human GPR34 and GPR174 in complex with LysoPS and Gi protein elucidated lipid-binding modes and structural features of the active state, providing mechanistic insights into ligand recognition and Gi-mediated signaling for this LysoPS receptor. Cryo-EM structure determination combined with functional studies PLoS biology High 38048360
2012 GPR34 acts as a Gi/o protein-coupled receptor whose overexpression in lymphoma and HeLa cells results in phosphorylation of ERK, PKC, and CREB, and induces CRE, AP1, and NF-κB-mediated gene transcription, leading to increased cell proliferation. The t(X;14)(p11.4;q32) IGH translocation deregulates GPR34 expression in marginal zone lymphoma. Overexpression in lymphoma/HeLa cells, phosphorylation assays, luciferase reporter assays, proliferation assays, FISH/molecular cloning of translocation Blood High 22966169
2021 GPR34 on ILC3s functions as a damage-sensing receptor for LysoPS released by apoptotic neutrophils. LysoPS stimulation of GPR34 activates ILC3s via downstream PI3K-AKT and ERK signaling to produce IL-22, promoting intestinal epithelial tissue repair. ILC3-specific deletion of Gpr34 or inhibition of PI3K-AKT/ERK suppressed IL-22 production in response to apoptotic neutrophils. ILC3-specific Gpr34 conditional knockout mice, co-culture experiments, metabolomic analyses identifying LysoPS, pharmacological inhibition of PI3K-AKT/ERK, colitis and skin injury models Immunity High 34107271
2010 GPR34 is a Gi protein-coupled receptor highly expressed in mononuclear immune cells. GPR34-deficient mice show altered immune responses including reduced granulocyte/macrophage accumulation after immunization, increased delayed-type hypersensitivity, higher pathogen burden after Cryptococcus neoformans infection, and altered cytokine levels (TNF-α, GM-CSF, IFN-γ), establishing GPR34 as functionally important in macrophage/immune cell responses. GPR34 knockout mouse line, immunization challenges, delayed-type hypersensitivity test, pulmonary infection model, cytokine measurements The Journal of biological chemistry High 21097509
2014 GPR34 deficiency in microglia results in morphological changes in retinal and cortical microglia and significantly reduced phagocytosis activity in both retina and acutely isolated cortical slices, without affecting microglial motility after lesion. RNA sequencing of GPR34-deficient microglia revealed differentially expressed transcripts involved in cell motility and phagocytosis. GPR34 knockout mice, RNA sequencing, microglial morphology analysis, phagocytosis assays in retina and cortical slices, laser lesion motility assay Glia High 25142016
2019 GPR34 is expressed by microglia in the spinal dorsal horn after sensory nerve injury and mediates neuropathic pain. GPR34-deficient mice showed attenuated nerve injury-induced pro-inflammatory cytokine expression and pain behaviors. LC-MS/MS detected LysoPS in the dorsal horn after nerve injury, and intrathecal administration of a GPR34 antagonist reduced neuropathic pain, establishing the LysoPS-GPR34 signaling axis in microglial pro-inflammatory responses underlying neuropathic pain. GPR34 knockout mice, in situ hybridization, von Frey test, LC-MS/MS quantification of LysoPS, intrathecal antagonist administration, qRT-PCR of cytokines Journal of neuroinflammation High 30975169
2024 GPR34 senses LysoPS derived from myelin debris to activate microglia and promote neuroinflammation via PI3K-AKT and ERK signaling pathways. LysoPS from myelin debris drove microglial pro-inflammatory cytokine production in a GPR34-dependent manner. In vivo, GPR34 inhibition (genetic or pharmacological) reduced neuroinflammation in mouse models of multiple sclerosis and stroke. GPR34 knockout mice, pharmacological GPR34 inhibition, EAE and stroke mouse models, cytokine measurement, signaling pathway analysis Cellular & molecular immunology High 39030423
2024 GPR34 expressed on ILC1s acts as a metabolic immune checkpoint: LysoPS enriched in the tumor microenvironment inhibits ILC1 antitumor activity via GPR34. Genetic deletion of LysoPS synthase Abhd16a in tumors, or Gpr34 in ILC1s, or pharmacological GPR34 antagonism enhanced ILC1 antitumor activity. ILC1-specific Gpr34 knockout, tumor Abhd16a knockout, GPR34 antagonist treatment, tumor models, functional ILC1 activity assays Nature immunology High 39358444
2024 LysoPS produced by ganglion cells activates the GPR34-PI3K-AKT-NINJ1 signaling axis in retinal microglia, upregulating inflammatory cytokines (IL-6, IL-8, VEGFA, FGF2) and promoting microglial extracellular trap formation and retinal neovascularization. Inhibition of the GPR34-PI3K-AKT-NINJ1 axis reduced these effects in vitro and in vivo. In vitro GPR34 signaling assays, cytokine measurement, in vivo mouse retinopathy model with GPR34 pathway inhibition Journal of neuroinflammation Medium 39468551
2016 A tri-basic motif in the first intracellular loop of GPR34 is the key topogenic signal that dictates the orientation of transmembrane domain-1 (TM1). Charge disruption of this motif perturbed topogenesis, caused loss of the conformational epitope, altered post-translational processing, and arrested trafficking in the Golgi. Placement of a cleavable N-terminal signal sequence as a surrogate topogenic determinant rescued TM1 orientation, conformational epitope, post-translational modifications, and cell surface trafficking. FLAG-tag and conformational epitope monitoring during mutant GPR34 expression, site-directed mutagenesis, N-terminal truncations, signal sequence insertion, Golgi trafficking assays Biochimica et biophysica acta High 27086875
2016 In dendritic cells, NF-κB and MAPK pathways are involved in the downregulation of GPR34 expression. DCs lacking GPR34 have higher caspase-3/7 activity and increased apoptosis levels, demonstrating a role for GPR34 in DC survival. RNA sequencing of GPR34 KO and WT mouse spleens and DCs, protein-protein interaction network analysis, pathway inhibitor experiments, caspase-3/7 activity assay, apoptosis assay Journal of immunology Medium 26851221
2018 GPR34 mutations in MALT lymphoma are predominantly nonsense and frameshift changes clustered in the C-terminal cytoplasmic tail, producing truncated proteins that lack the phosphorylation motif important for β-arrestin-mediated receptor desensitization and internalization, thus representing gain-of-function alterations. Whole exome sequencing of 21 MALT lymphoma cases, mutation screening, structural analysis of truncation effects on receptor desensitization motif Haematologica Medium 29674500
2022 The GPR34 Q340X truncation mutant confers significantly increased resistance to apoptosis and greater transforming potential than wild-type GPR34. The truncation mutant showed delayed internalization after LysoPS stimulation and significantly activated CRE, NF-κB, and AP1 reporter activities especially in the presence of ligand. Phospholipase-A1/2 activity in supernatant of GPR34 Q340X-expressing cells could catalyze LysoPS synthesis from phosphatidylserine. Isogenic Flp-InTRex293 cell lines with single-copy GPR34 or mutants, apoptosis assays, transformation assays, internalization assays, luciferase reporter assays, phospholipase activity measurement Blood High 34086889
2024 Phosphatidylserine phospholipase A1 (PLA1A) expressed by omental stromal fibroblasts generates lysoPS that acts on GPR34 to promote peritoneal accumulation of plasma cells and memory B cells. GPR34 knock-in B cells migrate robustly to lysoPS, and their maintenance in the peritoneal cavity depends on stromal PLA1A. GPR34 knock-in mouse allele, adoptive transfer, chimera experiments, ex vivo migration assays to lysoPS, PLA1A-deficient mice The Journal of experimental medicine High 39412501
2025 GPR34 on splenic cDC1s promotes uptake of apoptotic cells (efferocytosis) and cross-presentation of apoptotic cell-associated antigens to CD8 T cells. GPR34 deficiency reduced apoptotic cell uptake and OT-I T cell activation/proliferation, while GPR34 overexpression enhanced these functions. PLA1A, but not ABHD16A, deficiency impaired OT-I responses to apoptotic cell-associated antigen, identifying PLA1A as the relevant lysoPS-generating enzyme for this GPR34 function. GPR34 KO and overexpressing mice, apoptotic cell uptake assays, OT-I T cell proliferation assay, PLA1A and ABHD16A KO mice The Journal of experimental medicine High 41212150
2025 GPR34 is stabilized by the deubiquitinase USP8 in anaplastic thyroid carcinoma cells. Deletion of GPR34 promoted ferroptosis in ATC cells, and this effect was reversible by USP8 overexpression, establishing USP8 as a deubiquitinase that controls GPR34 protein levels. Co-immunoprecipitation/pulldown identifying USP8 as DUB for GPR34, GPR34 KO in vitro and in vivo, ferroptosis assays, USP8 overexpression rescue Mediators of inflammation Medium 40862294
2023 GPR34 knockdown in BV-2 microglia and APP/PS1 mice suppressed Aβ1-42-induced neuroinflammation via the ERK/NF-κB signaling pathway, reducing TNF-α, IL-1β, IL-6, and iNOS levels. GPR34 overexpression-induced ERK/NF-κB activation and cytokine upregulation was abolished by ERK inhibitor FR180204, placing GPR34 upstream of ERK in microglial inflammatory signaling. GPR34 knockdown and overexpression in BV-2 cells and APP/PS1 mice, ERK inhibitor epistasis, western blot, immunofluorescence, water maze cognitive testing Neuroscience Medium 37557947
2025 Selective GPR34 agonism (compound M1) enhances microglial phagocytosis of Aβ fibrils (but not monomers or oligomers) by reducing intracellular cAMP levels via Gi/o coupling. This enhancement required functional TREM2 signaling. Gpr34 knockdown confirmed GPR34 as the molecular target of M1. Flow cytometry-based Aβ uptake assays in mouse primary microglia and iPSC-derived human microglia, cAMP measurement, Gpr34 knockdown, intrahippocampal M1 injection in amyloid precursor protein knock-in mice Alzheimer's research & therapy High 41261421
2014 LysoPS stimulates chemotactic migration of colorectal cancer cells through GPR34 and the PI3K/Akt pathway. GPR34 was the most highly expressed LysoPS receptor on colorectal cancer cell lines. GPR34 knockdown and PI3K inhibitor wortmannin both inhibited LysoPS-induced migration. RT-PCR expression profiling, siRNA knockdown of GPR34, chemotaxis assay, PI3K inhibitor (wortmannin) treatment Anticancer research Medium 25275042
2005 GPR34 uses multiple translational start points from conserved in-frame AUGs within the first 150 bp of the coding region, with a preference for the second in-frame AUG in human GPR34. Combinatory mutagenesis and reporter construct expression confirmed these multiple translational initiation sites. Alternative splicing of a cryptic intron shortens the N-terminus by 47 amino acids. Combinatory mutagenesis, reporter construct expression, genomic analysis of multiple vertebrate species, identification of alternative splice site Genomics Medium 16338117
2025 In GPR34-deficient macrophages, LysoPS-GPR34 signaling promotes CXCL16 secretion and efferocytosis in a damage context. Enhanced efferocytosis by GPR34+ macrophages promoted MHC-I degradation via the lysosomal pathway, leading to CD8+ T cell exhaustion in pancreatic cancer. Gpr34-conditional KO (Gpr34ΔLyz2) mice, single-cell RNA sequencing, in vitro co-cultures, MHC-I degradation assays, CD8+ T cell exhaustion assays Signal transduction and targeted therapy Medium 42045172
2025 GPR34 knockout in microglia accelerates transition to disease-associated microglia (DAM) states in healthy and amyloid mouse models, and in 5xFAD × Gpr34 KO mice further exacerbates DAM profiles and glial pathology without affecting plaque burden. In iPSC-derived human microglia, GPR34 KO reduced Ca2+ and ERK phosphorylation in response to lysoPS and myelin, selectively impaired phagocytosis of myelin (but not Aβ or E. coli), and altered transcriptional responses to myelin. Global Gpr34 KO crossed with 5xFAD mice, RNA-seq, iPSC-derived microglia with GPR34 KO, Ca2+ signaling assays, pERK measurement, phagocytosis assays for multiple substrates bioRxivpreprint Medium
2025 GPR34 knockout in iPSC-derived microglia rescues dysregulated cholesterol metabolism seen in TREM2 KO microglia and promotes fatty acid catabolism. GPR34 agonism promotes ERK interaction and activation; GPR34 KO downregulates ERK signaling. In amyloid mouse models, Gpr34 KO accelerates homeostatic-to-DAM microglial conversion and is associated with increased large amyloid plaque frequency. GPR34 KO iPSC-derived microglia, TREM2 KO iPSC-derived microglia, metabolic assays, ERK co-immunoprecipitation, amyloid mouse model with Gpr34 KO bioRxivpreprint Medium

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 GPR34-mediated sensing of lysophosphatidylserine released by apoptotic neutrophils activates type 3 innate lymphoid cells to mediate tissue repair. Immunity 95 34107271
2010 Altered immune response in mice deficient for the G protein-coupled receptor GPR34. The Journal of biological chemistry 78 21097509
2014 Altered microglial phagocytosis in GPR34-deficient mice. Glia 72 25142016
2012 GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position. Journal of biochemistry 69 22343749
2018 Novel GPR34 and CCR6 mutation and distinct genetic profiles in MALT lymphomas of different sites. Haematologica 53 29674500
2019 GPR34 in spinal microglia exacerbates neuropathic pain in mice. Journal of neuroinflammation 50 30975169
2012 t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth. Blood 45 22966169
2015 Structure-activity relationships of lysophosphatidylserine analogs as agonists of G-protein-coupled receptors GPR34, P2Y10, and GPR174. Journal of medicinal chemistry 42 25970039
2018 The G protein-coupled receptor GPR34 - The past 20 years of a grownup. Pharmacology & therapeutics 35 29684466
2011 t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34. Haematologica 35 22058210
1993 PDGF-BB and TGF-alpha rescue gastrulation, spiculogenesis, and LpS1 expression in collagen-disrupted embryos of the sea urchin genus Lytechinus. Mechanisms of development 33 8155573
2014 Lysophosphatidylserine stimulates chemotactic migration of colorectal cancer cells through GPR34 and PI3K/Akt pathway. Anticancer research 32 25275042
2005 Genomic and supragenomic structure of the nucleotide-like G-protein-coupled receptor GPR34. Genomics 27 16338117
2012 The ligand specificity of the G-protein-coupled receptor GPR34. The Biochemical journal 26 22348703
1991 A G-string positive cis-regulatory element in the LpS1 promoter binds two distinct nuclear factors distributed non-uniformly in Lytechinus pictus embryos. Development (Cambridge, England) 26 1811948
1991 Structure and promoter activity of the LpS1 genes of Lytechinus pictus. Duplicated exons account for LpS1 proteins with eight calcium binding domains. The Journal of biological chemistry 24 2037596
2016 Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence. Journal of immunology (Baltimore, Md. : 1950) 23 26851221
2023 Cryo-EM structures of human GPR34 enable the identification of selective antagonists. Proceedings of the National Academy of Sciences of the United States of America 22 37733739
2022 GPR34 activation potentially bridges lymphoepithelial lesions to genesis of salivary gland MALT lymphoma. Blood 19 34086889
2017 Probing the Hydrophobic Binding Pocket of G-Protein-Coupled Lysophosphatidylserine Receptor GPR34/LPS1 by Docking-Aided Structure-Activity Analysis. Journal of medicinal chemistry 19 28715213
2024 GPR34 senses demyelination to promote neuroinflammation and pathologies. Cellular & molecular immunology 18 39030423
2024 GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity. Nature immunology 17 39358444
2020 MicroRNA-381 targets G protein-Coupled receptor 34 (GPR34) to regulate the growth, migration and invasion of human cervical cancer cells. Environmental toxicology and pharmacology 17 33086148
2013 GPR34 as a lysophosphatidylserine receptor. Journal of biochemistry 16 23389307
2023 GPR34 Knockdown Relieves Cognitive Deficits and Suppresses Neuroinflammation in Alzheimer's Disease via the ERK/NF-κB Signal. Neuroscience 14 37557947
2020 Possible involvement of PS-PLA1 and lysophosphatidylserine receptor (LPS1) in hepatocellular carcinoma. Scientific reports 14 32060356
2024 Structural basis for lysophosphatidylserine recognition by GPR34. Nature communications 13 38326347
2023 Structural basis for ligand recognition and signaling of the lysophosphatidylserine receptors GPR34 and GPR174. PLoS biology 10 38048360
2020 LPS1, Encoding Iron-Sulfur Subunit SDH2-1 of Succinate Dehydrogenase, Affects Leaf Senescence and Grain Yield in Rice. International journal of molecular sciences 10 33375756
2013 A Strategy Combining Differential Low-Throughput Screening and Virtual Screening (DLS-VS) Accelerating the Discovery of new Modulators for the Orphan GPR34 Receptor. Molecular informatics 10 27481282
2024 Ganglion cell-derived LysoPS induces retinal neovascularisation by activating the microglial GPR34-PI3K-AKT-NINJ1 axis. Journal of neuroinflammation 9 39468551
1997 An extracellular matrix response element in the promoter of the LpS1 genes of the sea urchin Lytechinus pictus. Nucleic acids research 8 9224621
2021 MicroRNA-300 Inhibits the Proliferation and Metastasis of Cervical Cancer Cells via Posttranscriptional Suppression of G Protein-Coupled Receptor 34 (GPR34). Journal of oncology 6 34950207
2016 Topogenesis and cell surface trafficking of GPR34 are facilitated by positive-inside rule that effects through a tri-basic motif in the first intracellular loop. Biochimica et biophysica acta 5 27086875
2000 Physical mapping and exclusion of GPR34 as the causative gene for congenital stationary night blindness type 1. Human genetics 5 10982042
1996 A tissue-specific repressor in the sea urchin embryo of Lytechinus pictus binds the distal G-string element in the LpS1-beta promoter. DNA and cell biology 5 8672248
2024 Phosphatidylserine phospholipase A1 enables GPR34-dependent immune cell accumulation in the peritoneal cavity. The Journal of experimental medicine 4 39412501
1996 Two distinct forms of USF in the Lytechinus sea urchin embryo do not play a role in LpS1 gene inactivation upon disruption of the extracellular matrix. Molecular reproduction and development 4 8873063
1996 USF in the Lytechinus sea urchin embryo may act as a transcriptional repressor in non-aboral ectoderm cells for the cell lineage-specific expression of the LpS1 genes. Journal of molecular biology 4 8950263
1996 A G/C-rich DNA-regulatory element controls positive expression of the sea urchin Lytechinus pictus aboral ectoderm-specific LpS1 gene. DNA and cell biology 3 8634141
2025 GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC. Mediators of inflammation 2 40862294
2025 Splenic cDC1 efferocytosis and cross-presentation to CD8 T cells are promoted by GPR34 and lysophosphatidylserine. The Journal of experimental medicine 2 41212150
2025 Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils. Alzheimer's research & therapy 2 41261421
2023 Discovery of (S)-3-(4-(benzyloxy)phenyl)-2-(2-phenoxyacetamido)propanoic acid derivatives as a new class of GPR34 antagonists. Bioorganic & medicinal chemistry letters 2 37949379
2026 Targeting GPR34 in damage-associated macrophages enhances anti-tumor immunity and the efficacy of Surufatinib in pancreatic cancer. Signal transduction and targeted therapy 0 42045172
2025 GPR34 inhibition reprograms tumor-associated macrophages and enhances the sensitivity of anti-PD-1 therapy in hepatocellular carcinoma. Cancer cell international 0 41272735