Affinage

PROK1

Prokineticin-1 · UniProt P58294

Length
105 aa
Mass
11.7 kDa
Annotated
2026-06-10
100 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PROK1 (EG-VEGF/prokineticin 1) is a secreted peptide that acts as an angiogenic and cell-fate regulator by binding the two G-protein-coupled receptors PROKR1 and PROKR2, triggering nanomolar transient intracellular calcium flux, p44/42 MAP kinase phosphorylation, and DNA synthesis (PMID:12054613). The two receptors partition its activities: PROKR1 transduces angiogenic and proliferative outputs—endothelial proliferation, migration, survival and sprouting (PMID:20587779), and trophoblast proliferation through the homeobox gene HLX (PMID:22941044)—whereas PROKR2 mediates endothelial permeability and paracellular transport (PMID:20587779) and the suppression of trophoblast migration and invasion via reduced MMP-2/MMP-9 production (PMID:19602057). In the placental decidua, PROK1 signals through PROKR1 to induce IL-11 via a Gq/11–ERK–calcium–calcineurin/NFAT cascade negatively regulated by RCAN1-4 (PMID:19801577), and to induce CTGF through a Gq–PLC–cSrc–EGFR–MEK/ERK pathway that promotes trophoblast adhesion and tube formation (PMID:21098624); PROKR1 localizes to primary cilia, where ciliogenesis (IFT88-dependent) is required for EG-VEGF–driven ERK activation, MMP induction, and trophoblast invasion (PMID:27736039). PROK1 expression and its receptors are induced upstream by hCG via cAMP/CRE elements in the EG-VEGF promoter (PMID:22138749) and by PPARγ activation (PMID:26081281). Beyond reproduction, PROK1 directs bone marrow cells toward the monocyte/macrophage lineage and reprograms monocyte cytokine output (PMID:15908459), and acts upstream of the PI3K/AKT/mTOR axis to sustain proliferation and survival in pancreatic carcinoma cells (PMID:30551529), with receptor antagonism limiting choriocarcinoma growth in vivo (PMID:28899975).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Establishing that PROK1 is a functional ligand for two specific GPCRs answered how this secreted peptide initiates signaling and links it to endothelial mitogenesis.

    Evidence Radioligand binding, calcium imaging in CHO cells expressing PROKR1/PROKR2, MAP kinase and DNA synthesis assays in endothelial cells

    PMID:12054613

    Open questions at the time
    • Did not separate which receptor drives which downstream output
    • No structural basis for ligand-receptor recognition
  2. 2005 Medium

    Demonstrating PROK1-driven monocyte/macrophage differentiation and cytokine reprogramming extended its role beyond angiogenesis into immune cell fate.

    Evidence In vitro bone marrow differentiation, flow cytometry, cytokine ELISA, tissue binding

    PMID:15908459

    Open questions at the time
    • Receptor mediating the myeloid effect not defined by mutagenesis
    • In vivo relevance not established
  3. 2005 Medium

    Showing direct mitogenic and anti-apoptotic activity on luteal endothelial cells and VEGF induction in steroidogenic cells linked PROK1 to ovarian vascular biology.

    Evidence Primary luteal endothelial cells; thymidine incorporation, MAPK assay, c-jun/fos RT-PCR, apoptosis under serum withdrawal

    PMID:16320832

    Open questions at the time
    • Receptor attribution based on expression profiling not knockdown
    • No in vivo confirmation
  4. 2009 High

    Dissecting the IL-11 induction pathway defined the PROKR1 intracellular cascade (Gq/11-ERK-Ca2+-calcineurin/NFAT) and its negative regulator RCAN1-4 in decidua.

    Evidence PROKR1-Ishikawa cells; pharmacological pathway inhibitors, RCAN1-4 overexpression, lentiviral miRNA knockdown in primary decidua

    PMID:19801577

    Open questions at the time
    • Physiological role of decidual IL-11 induction not established in vivo
  5. 2009 High

    Receptor-specific knockdown established that PROKR2 mediates PROK1 inhibition of trophoblast invasion through MMP-2/MMP-9 suppression.

    Evidence Villous explants and HTR-8/SVneo cells; invasion assays, gelatin zymography, PROKR2 siRNA

    PMID:19602057

    Open questions at the time
    • Mechanism linking PROKR2 to MMP transcription not resolved
  6. 2010 High

    Receptor-selective siRNA and antibodies partitioned PROK1 angiogenic functions to PROKR1 and permeability functions to PROKR2 in placental endothelium.

    Evidence Primary placental microvascular endothelial cells; proliferation/migration/survival/sprouting/permeability assays with PROKR1 vs PROKR2 knockdown and neutralizing antibodies

    PMID:20587779

    Open questions at the time
    • Divergent G-protein coupling underlying the receptor split not defined
  7. 2010 High

    Mapping CTGF induction through Gq-PLC-cSrc-EGFR-ERK defined how PROKR1 promotes trophoblast adhesion and tube formation.

    Evidence PROKR1-Ishikawa cells and decidua; pathway inhibitors, miRNA knockdown, adhesion and matrigel assays

    PMID:21098624

    Open questions at the time
    • Direct EGFR transactivation mechanism not biochemically resolved
  8. 2011 Medium

    Identifying hCG as an upstream inducer via cAMP/CRE elements placed PROK1 within hormonal control of placentation.

    Evidence Placental explants and trophoblasts; qPCR, Western, promoter-reporter, cAMP measurement, pathway inhibition

    PMID:22138749

    Open questions at the time
    • Specific CRE sites not validated by mutagenesis
  9. 2012 Medium

    Linking PROK1-driven trophoblast proliferation to HLX through PROKR1 identified a downstream transcriptional effector of the proliferative branch.

    Evidence Placental explants; thymidine incorporation, Ki67, receptor-specific siRNA, HLX measurement

    PMID:22941044

    Open questions at the time
    • How PROKR1 signaling regulates HLX transcriptionally not defined
  10. 2014 Medium

    Showing PROK1 decreases MMP-2/9 activity and raises PGDH in fetal membranes with gestational dynamics connected it to fetal membrane remodeling and labor onset.

    Evidence Human fetal membrane and chorion trophoblast explants; MMP activity assays, PGDH and receptor expression across gestation

    PMID:25122063

    Open questions at the time
    • Causal role in labor timing not tested
    • Receptor specificity not dissected
  11. 2015 High

    Integrating PPARγ as an upstream activator using knockout mice and antagonists positioned PROK1 as a downstream effector of PPARγ in placental vascularization and invasion control.

    Evidence Human trophoblasts and explants, PPARγ-null mouse placentas, PROKR1/PROKR2 antagonists across proliferation/migration/invasion/vascularization assays

    PMID:26081281

    Open questions at the time
    • Direct PPARγ binding to the EG-VEGF locus not shown
  12. 2016 Medium

    Localizing PROKR1 to primary cilia and showing IFT88-dependence of ERK/MMP activation revealed a ciliary requirement for the invasion-promoting branch.

    Evidence HTR-8/SVneo cells; immunofluorescence, IFT88 siRNA, ERK inhibition, invasion assays, MMP Western blots

    PMID:27736039

    Open questions at the time
    • How ciliary localization couples PROKR1 to ERK not defined
    • Single lab
  13. 2017 Medium

    Demonstrating receptor antagonism reduces choriocarcinoma growth in an in vivo model established PROK1 signaling as a therapeutic target in trophoblastic tumors.

    Evidence JEG3 cells; 2D/3D proliferation/migration/invasion, PROKR1/PROKR2 antagonists, in vivo placental injection model

    PMID:28899975

    Open questions at the time
    • Relative contributions of PROKR1 vs PROKR2 to tumor effect not separated
  14. 2018 Medium

    Placing PROK1 upstream of PI3K/AKT/mTOR in pancreatic carcinoma extended its proliferative/survival signaling role to a non-reproductive cancer.

    Evidence shRNA knockdown in PANC-1/BxPC-3; proliferation, cell cycle, apoptosis assays, phospho-PI3K/AKT/mTOR Western blots

    PMID:30551529

    Open questions at the time
    • No rescue experiment
    • Receptor mediating the effect not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular basis for divergent PROKR1 vs PROKR2 G-protein coupling and the structural determinants of ligand-receptor selectivity remain unresolved.
  • No structural model of PROK1 bound to either receptor
  • Mechanism dictating receptor-specific downstream outputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 2 GO:0060089 molecular transducer activity 1
Localization
GO:0005576 extracellular region 2 GO:0005929 cilium 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1474165 Reproduction 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 1
Partners
PROKR1PROKR2

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 EG-VEGF/prokineticin 1 (PROK1) and prokineticin 2 are cognate ligands of two orphan G-protein-coupled receptors, ZAQ (PK-R1/PROKR1) and I5E (PK-R2/PROKR2). Binding induces a transient increase in intracellular calcium concentration with nanomolar potency in CHO cells expressing either receptor, and provokes rapid phosphorylation of p44/42 MAP kinase and DNA synthesis in bovine adrenal capillary endothelial cells. Radioligand binding assays, intracellular calcium measurements in CHO cells expressing PROKR1/PROKR2, MAP kinase phosphorylation assays, DNA synthesis assay in endothelial cells Biochemical and biophysical research communications High 12054613
2005 PROK1/PK1 induces differentiation of murine and human bone marrow cells into the monocyte/macrophage lineage and modulates human peripheral blood monocyte function, causing morphological changes, down-regulation of B7-1, CD14, CCR5, and CXCR4, and elevated IL-12 and TNFα with reduced IL-10 production in response to LPS. In vitro bone marrow differentiation assay, flow cytometry, cytokine measurement (ELISA), morphological analysis; macrophage identified as in vivo cellular target by tissue section binding Journal of leukocyte biology Medium 15908459
2009 EG-VEGF inhibits extravillous trophoblast (EVT) migration, invasion, and tube-like organisation via its receptors PKR1 and PKR2. The inhibitory effect on invasion was supported by decreased MMP-2 and MMP-9 production. siRNA-mediated knockdown of PKR2 (but not PKR1) reversed EG-VEGF-induced inhibitory effects on trophoblast invasion. Human villous explants and HTR-8/SVneo cell line; migration/invasion assays; gelatin zymography for MMP-2/MMP-9; siRNA knockdown of PROKR2 Journal of cellular and molecular medicine High 19602057
2010 EG-VEGF (PROK1) stimulates proliferation, migration, and survival of placental microvascular endothelial cells (HPEC) and is more potent than VEGF in promoting sprouting and pseudovascular organisation. PROKR1 mediates EG-VEGF angiogenic effects (proliferation, migration, survival, sprouting), whereas PROKR2 mediates cellular permeability and paracellular transport. Primary placental microvascular endothelial cells and HUVEC; proliferation, migration, survival, spheroid sprouting, permeability assays; siRNA knockdown and neutralising antibodies targeting PROKR1 vs PROKR2 Molecular biology of the cell High 20587779
2011 hCG increases EG-VEGF, PROKR1, and PROKR2 mRNA and protein expression in placental explants and primary trophoblasts in a dose- and time-dependent manner via cAMP response elements in the EG-VEGF promoter. The hCG effects are transcriptional and post-transcriptional and mediated via cAMP. Placental explants and primary trophoblast cultures; qPCR; Western blot; promoter-reporter assay; cAMP measurement; pharmacological inhibition of cAMP pathway Cellular and molecular life sciences : CMLS Medium 22138749
2012 EG-VEGF increases trophoblast proliferation via the homeobox gene HLX, and this proliferative effect is mediated specifically through PROKR1 but not PROKR2. EG-VEGF also increases vascularization of placental villi and promotes their survival. Placental explants and primary trophoblast cultures; [³H]-thymidine incorporation; Ki67 staining; PROKR1/PROKR2-specific siRNA; HLX expression measurement Cellular and molecular life sciences : CMLS Medium 22941044
2009 PROK1 signals via PROKR1 to induce IL-11 expression through a Gq/11, ERK, Ca²⁺, calcineurin, and NFAT (calcineurin/NFAT) dependent pathway. RCAN1-4 (regulator of calcineurin 1 isoform 4) acts as a negative regulator of this pathway. Knockdown of endogenous PROK1 using lentiviral miRNA significantly reduced IL-11 expression and secretion in first-trimester decidua. PROKR1-Ishikawa cells; qPCR; ELISA; pharmacological inhibition of Gq, ERK, Ca²⁺, calcineurin/NFAT; adenoviral overexpression of RCAN1-4; lentiviral miRNA knockdown of PROK1 in decidua Molecular human reproduction High 19801577
2010 PROK1 regulates CTGF (connective tissue growth factor) expression in first-trimester decidua via the Gq, phospholipase C, cSrc, EGFR, MAPK/ERK kinase signalling pathway. CTGF in turn increases trophoblast adhesion to collagen IV and promotes tube-like structure formation. PROKR1-Ishikawa cells and first-trimester decidua; qPCR; Western blot; specific pathway inhibitors (Gq, PLC, cSrc, EGFR, MEK); miRNA constructs to knock down endogenous PROK1; HTR-8/SVneo adhesion and matrigel assays Human reproduction (Oxford, England) High 21098624
2016 EG-VEGF activates ERK1/2 signalling, leading to upregulation of MMP2 and MMP9, thereby facilitating trophoblast cell invasion. PROKR1 localizes to primary cilia, and depletion of IFT88 (blocking ciliogenesis) inhibits EG-VEGF-induced ERK1/2 activation, MMP upregulation, and trophoblast invasion. HTR-8/SVneo cells; ERK1/2 inhibition; IFT88 siRNA knockdown; immunofluorescence localization of PROKR1 to primary cilia; invasion assays; Western blot for MMP2/MMP9 Journal of cellular physiology Medium 27736039
2007 EG-VEGF (PROK1) and its receptors PKR1 and PKR2 are expressed in mouse placenta throughout gestation. EG-VEGF is mainly localised in the labyrinth layer (highest before E10.5 dpc), while PKR1 protein co-localises with EG-VEGF in the labyrinth and PKR2 is maintained over E10.5 dpc with both trophoblastic and endothelial cell localisations, indicating differential receptor engagement in distinct cell types. Mouse placental tissue; immunohistochemistry; qRT-PCR; Western blot at multiple gestational timepoints Placenta Medium 17531315
2015 PPARγ activation (rosiglitazone) increases EG-VEGF secretion and upregulates EG-VEGF, PROKR1, and PROKR2 expression in human trophoblasts and placental explants. PPARγ(-/-) mouse placentas have significantly decreased EG-VEGF levels. EG-VEGF mediates PPARγ effects on placental vascularization (via PROKR1 and PROKR2) and inhibition of trophoblast migration and invasion (via PROKR2). Human primary cytotrophoblasts; HTR-8/SVneo cells; placental explants; PPARγ(+/-) and PPARγ(-/-) mouse placentas; PROKR1/PROKR2 receptor antagonists; proliferation, migration, invasion, vascularization assays American journal of physiology. Endocrinology and metabolism High 26081281
2017 EG-VEGF increases JEG3 choriocarcinoma cell proliferation, migration, and invasion in 2D and 3D culture systems. Treatment with EG-VEGF receptor antagonists (targeting PROKR1/PROKR2) significantly reduced tumor development and progression in a novel in vivo choriocarcinoma mouse model (JEG3-luciferase injected into gravid SCID-mouse placenta). JEG3 cell line; 2D/3D culture proliferation, migration, invasion assays; PROKR1/PROKR2 antagonist treatment; in vivo placental injection CC mouse model; antibody-array and immunohistochemistry Clinical cancer research Medium 28899975
2005 EG-VEGF/PK-1 elevates [³H]-thymidine incorporation, activates MAPK, and induces c-jun/fos mRNA expression in luteal endothelial cells (LEC), demonstrating direct mitogenic activity. EG-VEGF/PK-1 also inhibits serum starvation-induced apoptosis in LEC. In bovine luteal steroidogenic cells (which express only PK-R1), EG-VEGF/PK-1 elevated VEGF mRNA expression. Primary luteal endothelial cells; [³H]-thymidine incorporation; MAPK activation assay; RT-PCR for c-jun/fos; apoptosis assay under serum withdrawal; receptor expression characterization Annals of anatomy Medium 16320832
2018 Knockdown of EG-VEGF (PROK1) in pancreatic carcinoma cells (PANC-1 and BxPC-3) inhibited cell proliferation, induced G0/G1 cell cycle arrest, and promoted apoptosis. EG-VEGF silencing significantly reduced phosphorylated PI3K, AKT, and mTOR levels, placing EG-VEGF upstream of the PI3K/AKT/mTOR signalling pathway in pancreatic cancer cells. shRNA lentiviral knockdown of PROK1; MTT proliferation assay; flow cytometry (cell cycle and apoptosis); Western blot for p-PI3K, p-AKT, p-mTOR Biomedicine & pharmacotherapy Medium 30551529
2014 EG-VEGF decreases metalloproteinase-2 and -9 activities and increases PGDH (prostaglandin-metabolising enzyme) expression in chorion trophoblast and fetal membrane explants. EG-VEGF and its receptors (PROKR1 and PROKR2) show increased expression in fetal membranes toward term with an abrupt decrease at the onset of labor. Human fetal membrane explants; primary chorion trophoblast cultures; MMP-2/MMP-9 activity assays; PGDH expression measurement; qRT-PCR and protein quantification across gestational timepoints Biology of reproduction Medium 25122063

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Isolation and identification of EG-VEGF/prokineticins as cognate ligands for two orphan G-protein-coupled receptors. Biochemical and biophysical research communications 183 12054613
1985 Biochemical characterization of renal epithelial cell cultures (LLC-PK1 and MDCK). The American journal of physiology 142 3985161
2000 Protein kinase C activation leads to dephosphorylation of occludin and tight junction permeability increase in LLC-PK1 epithelial cell sheets. Journal of cell science 133 10954417
2005 Ouabain-induced endocytosis of the plasmalemmal Na/K-ATPase in LLC-PK1 cells requires caveolin-1. Kidney international 117 15840032
1990 Regulation of glucose transporters in LLC-PK1 cells: effects of D-glucose and monosaccharides. Molecular and cellular biology 101 2247068
2005 Gentamicin-induced apoptosis in LLC-PK1 cells: involvement of lysosomes and mitochondria. Toxicology and applied pharmacology 97 16039943
2000 Specificity of doxorubicin versus rhodamine-123 in assessing P-glycoprotein functionality in the LLC-PK1, LLC-PK1:MDR1 and Caco-2 cell lines. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 96 11042226
1995 Cadmium-induced expression of immediate early genes in LLC-PK1 cells. Kidney international 87 7564105
2009 Role of EG-VEGF in human placentation: Physiological and pathological implications. Journal of cellular and molecular medicine 84 19602057
2010 Molecular characterization of EG-VEGF-mediated angiogenesis: differential effects on microvascular and macrovascular endothelial cells. Molecular biology of the cell 82 20587779
2005 PK1/EG-VEGF induces monocyte differentiation and activation. Journal of leukocyte biology 80 15908459
1997 Protein kinase C-alpha activity modulates transepithelial permeability and cell junctions in the LLC-PK1 epithelial cell line. The Journal of biological chemistry 79 9169467
1997 Advanced glycation endproducts stimulate the MAP-kinase pathway in tubulus cell line LLC-PK1. FEBS letters 72 9237687
2016 miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9. BioFactors (Oxford, England) 65 27619846
2002 Effects of cardiac glycosides on sodium pump expression and function in LLC-PK1 and MDCK cells. Kidney international 65 12427136
2011 Revisiting the role of hCG: new regulation of the angiogenic factor EG-VEGF and its receptors. Cellular and molecular life sciences : CMLS 63 22138749
2004 EG-VEGF and Bv8: a novel family of tissue-restricted angiogenic factors. Biochimica et biophysica acta 60 14984768
2003 Cyclic AMP reverses radiocontrast media-induced apoptosis in LLC-PK1 cells by activating A kinase/PI3 kinase. Kidney international 56 14633127
1998 Overexpression of protein kinase C-delta increases tight junction permeability in LLC-PK1 epithelia. The American journal of physiology 56 9688609
1998 Role of enhanced ceramide generation in DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells. Kidney international 56 9690206
1993 Cytoskeletal reorganization and TPA differently modify AP-1 to induce the urokinase-type plasminogen activator gene in LLC-PK1 cells. Nucleic acids research 56 8346015
2001 Inhibition of Na,K-ATPase activates PI3 kinase and inhibits apoptosis in LLC-PK1 cells. Biochemical and biophysical research communications 54 11437370
1995 Alterations in MDCK and LLC-PK1 cells exposed to oxalate and calcium oxalate monohydrate crystals. Scanning microscopy 54 8714751
2012 EG-VEGF controls placental growth and survival in normal and pathological pregnancies: case of fetal growth restriction (FGR). Cellular and molecular life sciences : CMLS 52 22941044
2016 Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion. Journal of cellular physiology 51 27736039
1998 Apoptosis and necrosis during ischaemia in renal tubular cells (LLC-PK1 and MDCK). Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 51 9623548
1998 Distinct localizations of tropomyosin isoforms in LLC-PK1 epithelial cells suggests specialized function at cell-cell adhesions. Cell motility and the cytoskeleton 51 9712268
1992 Influence of ammonia and pH on protein and amino acid metabolism in LLC-PK1 cells. Kidney international 50 1405337
1991 Regulation of taurine transporter activity in LLC-PK1 cells: role of protein synthesis and protein kinase C activation. Journal of the American Society of Nephrology : JASN 49 1760538
2003 EG-VEGF and Bv8. a novel family of tissue-selective mediators of angiogenesis, endothelial phenotype, and function. Trends in cardiovascular medicine 47 14522467
1990 Morphology of the differentiation and maturation of LLC-PK1 epithelia. Journal of cellular physiology 47 2303524
2003 Hsp27, Hsp70, and metallothionein in MDCK and LLC-PK1 renal epithelial cells: effects of prolonged exposure to cadmium. Toxicology and applied pharmacology 46 12915104
1998 Apical and basolateral uptake and intracellular fate of dopamine precursor L-dopa in LLC-PK1 cells. The American journal of physiology 45 9486218
2005 Cardiac glycoside downregulates NHE3 activity and expression in LLC-PK1 cells. American journal of physiology. Renal physiology 43 16352745
2007 Placental expression of EG-VEGF and its receptors PKR1 (prokineticin receptor-1) and PKR2 throughout mouse gestation. Placenta 42 17531315
2000 Gliotoxin-induced cytotoxicity proceeds via apoptosis and is mediated by caspases and reactive oxygen species in LLC-PK1 cells. Toxicological sciences : an official journal of the Society of Toxicology 41 10746946
1999 Pharmacokinetics of PK1 and doxorubicin in experimental colon tumor models with differing responses to PK1. Clinical cancer research : an official journal of the American Association for Cancer Research 41 10589787
1998 Advanced glycated albumin impairs protein degradation in the kidney proximal tubules cell line LLC-PK1. Cellular and molecular biology (Noisy-le-Grand, France) 41 9846887
1995 Cytotoxicity of mercury compounds in LLC-PK1, MDCK and human proximal tubular cells. Kidney international 41 7723229
2005 Characterization of polarized expression of point- or deletion-mutated human BCRP/ABCG2 in LLC-PK1 cells. Pharmaceutical research 40 15835752
1996 Endonuclease induced DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells. Kidney international 39 8821817
1988 Quiescent LLC-PK1 cells as a model for cis-diamminedichloroplatinum(II) nephrotoxicity and modulation by thiol rescue agents. Cancer research 39 2458831
2000 Oxalate-induced ceramide accumulation in Madin-Darby canine kidney and LLC-PK1 cells. Kidney international 38 10844609
1992 Polarized expression of Na+/H+ exchange activity in LLC-PK1/PKE20 cells: II. Hormonal regulation. Pflugers Archiv : European journal of physiology 38 1317951
1999 TGF-beta-activating kinase-1 inhibits cell cycle and expression of cyclin D1 and A in LLC-PK1 cells. Kidney international 36 10504490
1999 Heat shock protein 70 overexpression protects LLC-PK1 tubular cells from heat shock but not hypoxia. Kidney international 34 9893127
2002 EG-VEGF and the concept of tissue-specific angiogenic growth factors. Seminars in cell & developmental biology 33 11969366
1996 Expression of proximal tubular Na-Pi and Na-SO4 cotransporters in MDCK and LLC-PK1 cells by transfection. The American journal of physiology 32 8769843
1995 The relative roles of external taurine concentration and medium osmolality in the regulation of taurine transport in LLC-PK1 and MDCK cells. Pediatric research 32 7537366
1985 LLC-PK1 cysts: a model for the study of epithelial polarity. Journal of cellular physiology 32 4066772
2017 Antagonism of EG-VEGF Receptors as Targeted Therapy for Choriocarcinoma Progression In Vitro and In Vivo. Clinical cancer research : an official journal of the American Association for Cancer Research 30 28899975
1997 Disassociation of oxidant-induced ATP depletion and DNA damage from early cytotoxicity in LLC-PK1 cells. The American journal of physiology 30 9227633
2018 EG-VEGF silencing inhibits cell proliferation and promotes cell apoptosis in pancreatic carcinoma via PI3K/AKT/mTOR signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 30551529
2010 CTGF expression is up-regulated by PROK1 in early pregnancy and influences HTR-8/Svneo cell adhesion and network formation. Human reproduction (Oxford, England) 27 21098624
2009 Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway. Molecular human reproduction 27 19801577
1995 Signaling and growth responses of LLC-PK1/Cl4 cells transfected with the rabbit AT1 ANG II receptor. The American journal of physiology 27 7733240
2015 PPARγ controls pregnancy outcome through activation of EG-VEGF: new insights into the mechanism of placental development. American journal of physiology. Endocrinology and metabolism 26 26081281
2014 Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss. Journal of assisted reproduction and genetics 26 24671265
2007 Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) expression in colorectal cancer. Journal of surgical oncology 26 17786959
2004 A prostacyclin analog beraprost sodium attenuates radiocontrast media-induced LLC-PK1 cells injury. Kidney international 26 15086904
1999 Cell cycle inhibitors (p27Kip1 and p21CIP1) cause hypertrophy in LLC-PK1 cells. Kidney international 26 10432388
2007 Expression and localization of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in human pancreas and pancreatic adenocarcinoma. The Journal of steroid biochemistry and molecular biology 24 17683928
2005 Unique expression and regulatory mechanisms of EG-VEGF/prokineticin-1 and its receptors in the corpus luteum. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 24 16320832
2001 Prostaglandin D(2) synthase induces apoptosis in pig kidney LLC-PK1 cells. Kidney international 24 11703586
1994 Apically and basolaterally internalized aminoglycosides colocalize in LLC-PK1 lysosomes and alter cell function. The American journal of physiology 24 8304430
1992 Functional localization of adenosine receptor-mediated pathways in the LLC-PK1 renal cell line. The American journal of physiology 24 1329540
1992 Ammoniagenesis in LLC-PK1 cultures: role of transamination. The American journal of physiology 24 1636683
1998 Molecular cloning and functional expression of an LLC-PK1 cell taurine transporter that is adaptively regulated by taurine. Advances in experimental medicine and biology 23 9635040
1995 Cell division does not increase transepithelial permeability of LLC-PK1 cell sheets. Experimental cell research 23 7556454
1995 Differential expression of multiple glutaminase mRNAs in LLC-PK1-F+ cells. The American journal of physiology 23 7573485
1986 LLC-PK1 cell mutants in cAMP metabolism respond normally to phorbol esters. FEBS letters 22 3017754
2009 The parathyroid hormone 1 receptor directly binds to the FERM domain of ezrin, an interaction that supports apical receptor localization and signaling in LLC-PK1 cells. Molecular endocrinology (Baltimore, Md.) 21 19608645
2007 Phosphoinositide 3-kinase is required for high glucose-induced hypertrophy and p21WAF1 expression in LLC-PK1 cells. Kidney international 21 17332736
1998 Functional and molecular evidence for P2X receptors in LLC-PK1 cells. The American journal of physiology 21 9841498
1997 Mechanisms of homologous and heterologous desensitization of PTH/PTHrP receptor signaling in LLC-PK1 cells. The American journal of physiology 21 9277393
1991 Distribution and structure of the vacuolar H+ ATPase in endosomes and lysosomes from LLC-PK1 cells. Experimental cell research 21 1824836
1987 Apical trehalase expression associated with cell patterning after inducer treatment of LLC-PK1 monolayers. Journal of cellular physiology 21 3298285
2004 EG-VEGF: a novel mediator of endocrine-specific angiogenesis, endothelial phenotype, and function. Annals of the New York Academy of Sciences 20 15153419
1997 Tubular toxicity of cyclosporine A and the influence of endothelin-1 in renal cell culture models (LLC-PK1 and MDCK). Pediatric nephrology (Berlin, Germany) 20 9438665
1996 Studies of renal injury. II. Activation of the glucose transporter 1 (GLUT1) gene and glycolysis in LLC-PK1 cells under Ca2+ stress. The Journal of clinical investigation 20 8755650
1995 LLC-PK1 epithelia as a model for in vitro assessment of proximal tubular nephrotoxicity. In vitro cellular & developmental biology. Animal 20 7735573
2013 Autographa californica multiple nucleopolyhedrovirus PK-1 is essential for nucleocapsid assembly. Virology 19 23768784
2003 Up-regulation of MDR1 function and expression by cisplatin in LLC-PK1 cells. Biological & pharmaceutical bulletin 19 12576681
1999 Cisplatin-induced toxicity in LLC-PK1 kidney epithelial cells: role of basolateral membrane transport. Toxicology letters 19 10403667
1992 Hypoxia-mediated impaired differentiation by LLC-PK1 cells: evidence based on the protein kinase C profile. Kidney international 19 1453599
2012 Effects of EG-VEGF, VEGF and TGF-β1 on pregnancy outcome in patients undergoing IVF-ET treatment. Journal of assisted reproduction and genetics 18 22847371
2005 Regulation of TauT by cisplatin in LLC-PK1 renal cells. Pediatric nephrology (Berlin, Germany) 18 15942793
2000 Mercury chloride activates c-Jun N-terminal kinase and induces c-jun expression in LLC-PK1 cells. Toxicological sciences : an official journal of the Society of Toxicology 18 10696784
1989 Pathways and regulation of ammoniagenesis by the LLC-PK1 cells in culture. The Journal of laboratory and clinical medicine 18 2570115
2020 Preventive Effect of Muscone against Cisplatin Nephrotoxicity in LLC-PK1 Cells. Biomolecules 17 33076219
2018 Telocinobufagin and Marinobufagin Produce Different Effects in LLC-PK1 Cells: A Case of Functional Selectivity of Bufadienolides. International journal of molecular sciences 17 30223494
1997 Tyrosine phosphorylation in DNA damage and cell death in hypoxic injury to LLC-PK1 cells. Kidney international 17 9186862
1994 Isoproterenol induces mitogenesis in MCT and LLC-PK1 tubular cells. Journal of the American Society of Nephrology : JASN 17 7919153
1994 Role of cell density/cell-cell contact, and growth state in expression of differentiated properties by the LLC-PK1 cell. Journal of cellular physiology 17 8163571
1998 Inhibition of cell differentiation by G alpha q in the renal epithelial cell line LLC-PK1. The American journal of physiology 16 9575800
1997 Chronic hypoxia induces LLC-PK1 cell proliferation and dedifferentiation by the activation of protein kinase C. The American journal of physiology 16 9227643
1991 cAMP stimulates protein kinase C activity in cultured renal LLC-PK1 cells. The American journal of physiology 16 1661084
2014 Endocrine gland-derived endothelial growth factor (EG-VEGF) is a potential novel regulator of human parturition. Biology of reproduction 15 25122063
1991 Receptor-mediated increase in cytosolic calcium in LLC-PK1 cells by platelet activating factor and thromboxane A2. Kidney international 15 1662319
1988 Sodium butyrate increases glucose transporter expression in LLC-PK1 cells. Proceedings of the National Academy of Sciences of the United States of America 15 3186708

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