Affinage

PRLR

Prolactin receptor · UniProt P16471

Length
622 aa
Mass
69.5 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRLR is a prolactin receptor that couples ligand binding to intracellular signaling through a pre-formed receptor dimer: PRL binding induces a conformational change in the pre-existing PRLr dimer that activates the receptor-associated JAK2 kinase and drives STAT5 phosphorylation, the canonical output that governs cell proliferation, differentiation, apoptosis, and metabolism (PMID:34715089, PMID:23940279). The membrane-proximal ligand-binding domain is the critical determinant of PRL binding and JAK2-STAT5 activation, and truncation of the C-terminal cytoplasmic region uncouples the receptor from JAK2/STAT5 signaling (PMID:39114445, PMID:34715089). Beyond membrane signaling, nuclear-localized PRLr functions as a transcriptional coactivator: ligand-induced phosphorylation activates a transactivation domain that recruits HMGN2 to facilitate STAT5a promoter binding and transcription, promoting anchorage-independent growth (PMID:21816901). Through JAK2-STAT5, PRLR regulates diverse physiological programs including hepatic insulin sensitivity (PMID:23775766), mammary epithelial proliferation and milk protein/fat synthesis (PMID:31369265), luteal progesterone production required for implantation and decidualization (PMID:10803598), and hippocampal neuronal apoptosis (PMID:31545956). PRLR abundance is controlled post-translationally by opposing ubiquitination and deubiquitination: AMPK-driven, β-TrCP-mediated ubiquitination targets the receptor for endocytic lysosomal degradation under energy deficiency (PMID:35248054), while CSN5 deubiquitinates and stabilizes PRLR to restore JAK2/STAT5 output (PMID:34424219); PRLR mRNA is additionally targeted by miR-142-3p (PMID:31369265). A short isoform (PRLR-SF) signals non-canonically by directly engaging NEK9 to activate Hippo signaling, with downstream TEAD1 repressing the pentose phosphate pathway enzymes G6PD and TKT to suppress nucleotide biosynthesis in pancreatic cancer (PMID:33664869). A gain-of-function intracellular-domain variant (Asn492Ile) selectively hyperactivates PI3K-Akt signaling and proliferation without affecting STAT5 (PMID:30445560).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Established that the implantation and decidualization phenotype of PRLR loss is an endocrine, ovary-driven effect rather than a direct uterine receptor requirement, placing PRLR upstream of luteal progesterone.

    Evidence PRLR knockout mouse with progesterone rescue and downstream implantation-gene readouts

    PMID:10803598

    Open questions at the time
    • Does not define the PRLR signaling pathway in luteal cells that drives progesterone production
    • Does not address direct uterine PRLR roles in other species
  2. 2009 Low

    Defined the activation mechanism as conformational change within a pre-existing PRLr dimer triggering JAK2 activation, reframing receptor activation away from ligand-induced dimerization.

    Evidence Review of biochemical receptor dimerization/Jak2 activation studies and cyclophilin A interaction

    PMID:19535262

    Open questions at the time
    • Review summary; specific experimental detail of cyclophilin A interaction not given
    • Structural basis of the activating conformational change not resolved
  3. 2011 Medium

    Revealed a non-membrane function: nuclear PRLr acts as a STAT5a transcriptional coactivator via a ligand-activated transactivation domain recruiting HMGN2.

    Evidence Co-IP, nuclear fractionation, promoter luciferase, and gain/loss-of-function in breast cancer cells

    PMID:21816901

    Open questions at the time
    • Mechanism of PRLr nuclear translocation not defined
    • Single-lab finding without independent replication
  4. 2013 Medium

    Connected PRLR-STAT5 signaling to systemic metabolism, showing hepatic PRLR controls insulin sensitivity and is itself regulated by nutrient sensing.

    Evidence Adenoviral overexpression/knockdown in vivo, db/db model, GCN2/mTOR/S6K1 pathway dissection

    PMID:23775766

    Open questions at the time
    • Hepatocyte-specific STAT5 target genes mediating insulin sensitivity not identified
    • Relevance to human insulin resistance untested
  5. 2013 Medium

    Demonstrated that a C-terminally truncated PRLR isoform can still couple to STAT5, establishing that distal domains are dispensable for some signaling.

    Evidence STAT5-luciferase reporter and western blot in HepG2 cells with chicken dPRLR

    PMID:23940279

    Open questions at the time
    • Avian ortholog; mammalian generalizability unclear
    • Functional consequences of the missing tail not characterized
  6. 2016 Medium

    Clarified receptor oligomerization, showing GHR and PRLR form higher-order assemblies of independent homodimers with distinct ligand-induced conformational responses.

    Evidence Split luciferase complementation and Co-IP in T47D cells

    PMID:27003442

    Open questions at the time
    • Functional signaling consequence of GHR-PRLR hetero-assemblages not resolved
    • Single-lab finding
  7. 2019 Medium

    Identified a gain-of-function intracellular-domain variant that selectively biases PRLR toward PI3K-Akt rather than STAT5, linking PRLR to pathway-specific dysregulation.

    Evidence In vitro mutagenesis, pAkt/pSTAT5 western blots, proliferation assays, Akt/mTOR inhibitor rescue

    PMID:30445560

    Open questions at the time
    • Structural basis for pathway-selective bias unknown
    • Disease causation established only by association, not in vivo
  8. 2019 Medium

    Defined miR-142-3p as a direct post-transcriptional regulator of PRLR controlling mammary proliferation and milk synthesis through mTOR/SREBP1/cyclin D1/STAT5.

    Evidence miRNA knockdown/overexpression in vitro and in vivo, western blot, cell cycle and lipid/protein readouts

    PMID:31369265

    Open questions at the time
    • Direct miR-142-3p:PRLR 3'UTR binding site not detailed here
    • Crosstalk between the multiple downstream pathways not dissected
  9. 2019 Medium

    Placed PRLR-JAK2-STAT5 signaling in neuronal apoptosis, showing bidirectional control of hippocampal neuron death and BDNF in a depression model.

    Evidence Lentiviral knockdown/overexpression in CMS mouse model, western blot, cleaved Caspase-3 immunofluorescence

    PMID:31545956

    Open questions at the time
    • Source and identity of the activating ligand in brain not defined
    • Single-lab, single disease model
  10. 2021 High

    Uncovered a non-canonical short-isoform pathway in which PRLR-SF engages NEK9 to activate Hippo signaling and suppress pentose phosphate flux via TEAD1-controlled G6PD/TKT.

    Evidence Co-IP, PLA, ChIP, promoter luciferase, 13C metabolite tracing, LC-MS, xenografts

    PMID:33664869

    Open questions at the time
    • How PRLR-SF activates NEK9 mechanistically is unresolved
    • Ligand dependence of the PRLR-SF/NEK9 axis unclear
  11. 2021 Medium

    Defined opposing post-translational stability control: CSN5-mediated deubiquitination stabilizes PRLR and restores JAK2/STAT5 output, under GATA1 transcriptional control.

    Evidence Co-IP, CSN5 shRNA, luciferase reporter, RT-PCR, immunofluorescence in GT1-7 cells

    PMID:34424219

    Open questions at the time
    • Direct CSN5 deubiquitinase activity on PRLR not biochemically isolated
    • Studied in the context of a herbal decoction treatment
  12. 2021 Medium

    Mapped the membrane-proximal ligand-binding domain as the critical site for PRL binding and JAK2-STAT5 activation via domain-deletion.

    Evidence STAT5-luciferase reporter with wild-type and domain-deletion PRLR mutant, recombinant PRL, in turtle ortholog

    PMID:34715089

    Open questions at the time
    • Non-mammalian ortholog; mammalian domain requirements may differ
    • Binding affinity not quantified
  13. 2021 Low

    Linked PRLR-JAK2-STAT5 to adipocyte lipid accumulation in an insulin resistance model.

    Evidence PRLR overexpression in SW872 adipocytes, p-JAK2/p-STAT5 western blot, triglyceride assay

    PMID:36238467

    Open questions at the time
    • Companion paper retracted; results uncertain
    • Single cell model without in vivo validation
  14. 2021 Medium

    Established that C-terminal truncation of PRLR (slick-hair alleles) eliminates JAK2/STAT5 coupling and confers thermotolerance, demonstrating the physiological consequence of cytoplasmic-tail loss.

    Evidence CRISPR/Cas9 editing of PRLR in cattle with thermoregulation, growth, and reproductive phenotyping

    PMID:39114445

    Open questions at the time
    • Molecular signaling profile of the truncated receptor not directly assayed in this study
    • Bovine context; human relevance unaddressed
  15. 2023 Medium

    Showed isoform-specific control of granulosa cell survival, where prolactin downregulation of both L- and S-PRLR drives oxidative stress, mitochondrial dysfunction, and autophagy-linked apoptosis.

    Evidence siRNA/overexpression of L- and S-PRLR, ROS, mitochondrial complex activity, ATP, apoptosis flow cytometry

    PMID:37833858

    Open questions at the time
    • Signaling pathway linking PRLR isoforms to mitochondrial function not defined
    • Ovine ortholog context
  16. 2023 Medium

    Identified a context where PRLR suppresses JAK/STAT3 signaling, with PRLR as a miR-181a-5p target controlling MSC immunomodulation.

    Evidence siRNA/overexpression of PRLR, STAT3 inhibitor, luciferase reporter, in vivo periodontitis model

    PMID:37490712

    Open questions at the time
    • Mechanism by which PRLR represses STAT3 not defined
    • Apparent opposition to canonical STAT activation unreconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PRLR balances canonical JAK2-STAT5, PI3K-Akt, nuclear coactivation, and short-isoform Hippo signaling within a single cell, and what determines pathway selection, remains unresolved.
  • No structural model integrating ligand binding with pathway-selective output
  • Determinants of isoform- and context-specific signaling not defined
  • Mechanism of PRLr nuclear import not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
BTRCCSN5GHRHMGN2JAK2NEK9STAT5A

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 The prolactin receptor (PRLr) localizes to the nucleus where it functions as a transcriptional coactivator through interactions with STAT5a and HMGN2. A novel transactivation domain within PRLr is activated by ligand-induced phosphorylation, which enables HMGN2 binding; this PRLr/HMGN2 association facilitates Stat5a-responsive promoter binding and transcriptional activation, promoting anchorage-independent growth. Co-immunoprecipitation, nuclear fractionation, promoter luciferase assay, loss-of-function and overexpression experiments in breast cancer cells Molecular endocrinology (Baltimore, Md.) Medium 21816901
2016 GHR and PRLR form higher-order hetero-assemblages composed of GHR homodimers and PRLR homodimers (not GHR-PRLR heterodimers). Both receptors pre-homodimerize independently of ligand; GH or PRL augments PRLR-PRLR complementation, whereas both ligands cause decline in GHR-PRLR hetero-complementation, indicating distinct conformational responses in homomers versus heteromers. Split luciferase complementation assay (bioluminescence resonance), co-immunoprecipitation in T47D breast cancer cells Molecular endocrinology (Baltimore, Md.) Medium 27003442
2013 Hepatic PRLR regulates insulin sensitivity via the STAT5 signaling pathway. Adenoviral overexpression of PRLR improved insulin sensitivity in mice, while knockdown impaired it; STAT5 pathway activation was required for this effect. PRLR expression was decreased under insulin-resistant (db/db) and increased under insulin-sensitive (leucine deprivation) conditions, with leucine deprivation upregulating PRLR via a GCN2/mTOR/S6K1-dependent pathway. Adenoviral overexpression and knockdown in vivo, in vitro cell assays, pathway inhibition experiments, db/db mouse model Diabetes Medium 23775766
2021 The short isoform of PRLR (PRLR-SF) suppresses the pentose phosphate pathway and nucleotide biosynthesis in pancreatic cancer by activating Hippo signaling. NEK9 directly interacts with PRLR-SF and acts as an intermediary between PRLR-SF and the Hippo pathway; downstream TEAD1 directly regulates expression of PPP rate-limiting enzymes G6PD and TKT. Co-immunoprecipitation, proximity ligation assay, chromatin immunoprecipitation, promoter luciferase assay, 13C-labeled metabolite tracing, LC-MS, subcutaneous and orthotopic xenograft models Theranostics High 33664869
2019 PRLR gene silencing inhibits hippocampal neuron apoptosis in a chronic mild stress depression model by inactivating the JAK2-STAT5 signaling pathway and elevating BDNF expression; conversely, PRLR overexpression promoted apoptosis through activation of JAK2-STAT5 and increased Caspase-3/Bax. Lentiviral shRNA knockdown and overexpression in vivo (CMS mouse model), western blot for pathway components, immunofluorescence for cleaved Caspase-3 Brain research Medium 31545956
2022 AMPK activation promotes ubiquitination of PrlR through the E3 ligase β-TrCP, leading to lysosomal degradation of PrlR via endocytosis, which attenuates prolactin signaling and inhibits milk protein synthesis under energy-deficient conditions. Pharmacological AMPK activation/inhibition, ubiquitination assay, lysosomal inhibitor experiments, in vitro mammary cell and in vivo mouse lactation models Cell communication and signaling : CCS Medium 35248054
2019 miR-142-3p directly targets PRLR mRNA; knockdown of miR-142-3p increases PRLR expression and activates downstream mTOR, SREBP1, cyclin D1, and STAT5 signaling, promoting mammary epithelial cell proliferation and milk fat/protein synthesis, while overexpression of miR-142-3p has the opposite effects. miRNA knockdown and overexpression in vitro and in vivo (mouse mammary gland), western blot, flow cytometry for cell cycle/apoptosis, triglyceride and β-casein measurements Journal of agricultural and food chemistry Medium 31369265
2019 PRLR variant Asn492Ile (located in the intracellular domain) increases prolactin-induced pAkt signaling (>1.3-fold) and cellular proliferation (1.4-fold) compared to wild-type PRLR, without affecting pSTAT5 signaling. Treatment with an Akt1/2 inhibitor or everolimus reduced Asn492Ile signaling and proliferation to wild-type levels, identifying this as a gain-of-function variant selectively activating the PI3K-Akt pathway. In vitro transfection and signaling assays (western blot for pAkt and pSTAT5), cell proliferation assays, pharmacological pathway inhibition Human molecular genetics Medium 30445560
2000 Implantation and decidualization defects in PRLR-deficient mice are mediated by insufficient ovarian (luteal) progesterone production, not by absence of uterine PRLR. Progesterone administration rescued implantation failure and restored expression of implantation-specific genes (LIF, amphiregulin, HB-EGF, COX-1/2, PPARδ, Hoxa-10, cyclin-D3, VEGF, Flk-1, neuropilin-1) in PRLR-/- mice. PRLR knockout mouse model, hormone rescue experiments, in situ hybridization and immunolocalization, gene expression analysis Endocrinology High 10803598
2009 PRL binding induces conformational change of a pre-existing PRLr dimer complex that is necessary for activation of PRLr-associated Jak2 kinase. Cyclophilin A (a prolyl isomerase) plays a role in ligand-induced activation of PRLr-associated Jak2. Biochemical/functional analyses of receptor dimerization and Jak2 activation reviewed from primary studies; cyclophilin A interaction studies Trends in endocrinology and metabolism: TEM Low 19535262
2021 The slick-hair phenotype in cattle is caused by mutations in PRLR that truncate the C-terminal region of the protein involved in JAK2/STAT5 activation during prolactin signaling. CRISPR/Cas9-introduced SLICK1 variants conferred superior thermoregulation, growth, and scrotal circumference without deleterious effects on reproduction or carcass characteristics. CRISPR/Cas9 gene editing of PRLR in Angus and Jersey cattle, physiological measurements (vaginal/rectal temperature), growth and reproductive phenotyping FASEB bioAdvances Medium 39114445
2021 PRLR-mediated JAK2/STAT5 signaling promotes lipid (triglyceride) accumulation in adipocytes; PRLR overexpression in an insulin resistance cell model increased TG content and phosphorylated JAK2 and STAT5 levels. (Note: the companion paper PMID 38077883 was retracted; this finding from PMID 36238467 remains, though caution is warranted.) Western blot for PRLR, p-JAK2, p-STAT5; triglyceride colorimetric assay; PRLR overexpression in SW872 adipocytes with oleic acid-induced insulin resistance model Computational and mathematical methods in medicine Low 36238467
2021 In Chinese soft-shelled turtle, the membrane-proximal ligand-binding domain of PRLR is the critical domain for PRL binding and receptor activation; a PRLR mutant lacking the membrane-distal ligand-binding domain (PRLR-M2) could still be dose-dependently activated by recombinant PRL and trigger the intracellular JAK2-STAT5 signaling cascade. 5× STAT5-luciferase reporter system with wild-type PRLR and domain-deletion mutant (PRLR-M2), recombinant PRL protein expressed in E. coli General and comparative endocrinology Medium 34715089
2013 The duplicated PRLR gene (dPRLR) at the chicken K locus encodes a functional PRL receptor lacking a 149-aa C-terminal tail; when expressed in HepG2 cells it can be activated by chicken PRL and couples to the intracellular STAT5 signaling pathway. 5× STAT5-luciferase reporter system, western blot, RT-PCR expression analysis in HepG2 cells transfected with dPRLR Journal of molecular endocrinology Medium 23940279
2021 PRLR gene silencing in a CMS depression model reduced JAK2-STAT5 pathway activity and decreased expression of Caspase-3 and Bax in hippocampal CA3 neurons, with increased BDNF and Bcl-2, establishing that PRLR signals through JAK2-STAT5 to regulate neuronal apoptosis in this context. Lentiviral PRLR shRNA and overexpression in CMS mouse model, western blot for pathway and apoptotic markers, immunofluorescence Brain research Medium 31545956
2021 Bu-Shen-Zhu-Yun Decoction promotes PRLR deubiquitination via CSN5 (COP9 signalosome subunit 5), increasing PRLR protein levels and restoring JAK2/STAT5 phosphorylation and kisspeptin expression in hyperprolactinemia-treated GT1-7 cells. GATA1 transcriptionally regulates CSN5, and BSZY-D increases GATA1 binding to the CSN5 promoter. Co-immunoprecipitation, western blot, RT-PCR, renilla luciferase reporter assay, shRNA knockdown of CSN5, immunofluorescence Aging Medium 34424219
2023 High prolactin concentrations induce apoptosis in ovine ovarian granulosa cells by downregulating both L-PRLR and S-PRLR, activating oxidative stress (increased ROS, decreased mitochondrial respiratory chain complex activity and ATP), and inducing autophagy (ATG7/ATG5 upregulation). Knockdown of either L-PRLR or S-PRLR further reduced mitochondrial function, while overexpression had the opposite effect. siRNA knockdown and overexpression of L-PRLR and S-PRLR in granulosa cells, ROS measurement, mitochondrial respiratory complex activity assay, ATP measurement, flow cytometry for apoptosis International journal of molecular sciences Medium 37833858
2023 In mandibular BM-MSCs, PRLR is a downstream target of miR-181a-5p; activation of JAK/STAT3 signaling occurs when PRLR is knocked down or when miR-181a-5p mimics are transfected, impairing immunomodulatory function. PRLR overexpression enhanced in vivo immunosuppressive properties of BM-MSCs in a periodontitis model, suggesting PRLR normally suppresses JAK/STAT3 in this context. siRNA and overexpression of PRLR in BM-MSCs, STAT3 inhibitor treatment, luciferase reporter assay for miR-181a-5p/PRLR interaction, in vivo periodontitis mouse model Aging Medium 37490712

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Ovarian steroids differentially regulate the expression of PRL-R in neuroendocrine dopaminergic neuron populations: a double label confocal microscopic study. Brain research 97 9748546
1992 Detection of prolactin receptor (PRL-R) mRNA in the rat hypothalamus and pituitary gland. Endocrinology 94 1537321
2009 New mechanisms for PRLr action in breast cancer. Trends in endocrinology and metabolism: TEM 80 19535262
2008 Partial duplication of the PRLR and SPEF2 genes at the late feathering locus in chicken. BMC genomics 80 18713476
2021 Crosstalk between PRLR and EGFR/HER2 Signaling Pathways in Breast Cancer. Cancers 59 34572912
2000 Implantation and decidualization defects in prolactin receptor (PRLR)-deficient mice are mediated by ovarian but not uterine PRLR. Endocrinology 58 10803598
2013 PRLR regulates hepatic insulin sensitivity in mice via STAT5. Diabetes 51 23775766
2014 Prolactin (PRL) and prolactin receptor (PRLR) genes and their role in poultry production traits. Folia biologica 42 24745142
2021 The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer. Theranostics 41 33664869
2019 Reducing PRLR expression and JAK2 activity results in an increase in BDNF expression and inhibits the apoptosis of CA3 hippocampal neurons in a chronic mild stress model of depression. Brain research 41 31545956
2011 Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr) expression at dioestrus, pregnancy and normal and induced parturition. Reproductive biology and endocrinology : RB&E 41 21812980
2020 A novel bispecific antibody targeting CD3 and prolactin receptor (PRLR) against PRLR-expression breast cancer. Journal of experimental & clinical cancer research : CR 40 32398042
2007 A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: the multiethnic cohort. BMC medical genetics 40 18053149
2013 Molecular pathways: blockade of the PRLR signaling pathway as a novel antihormonal approach for the treatment of breast and prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 37 23515410
1996 Localization of ZNF164, ZNF146, GGTA1, SOX2, PRLR and EEF2 on homoeologous cattle, sheep and goat chromosomes by fluorescent in situ hybridization and comparison with the human gene map. Cytogenetics and cell genetics 32 8641144
2006 High amino acid variation in the intracellular domain of the pig prolactin receptor (PRLR) and its relation to ovulation rate and piglet survival traits. Journal of animal science 31 16864857
2023 Prolactin receptor signaling: A novel target for cancer treatment - Exploring anti-PRLR signaling strategies. Frontiers in endocrinology 28 36714582
2015 Single-nucleotide polymorphisms g.151435C>T and g.173057T>C in PRLR gene regulated by bta-miR-302a are associated with litter size in goats. Theriogenology 28 25799469
2008 Differences in prolactin receptor (PRLR) in mouse and human fallopian tubes: evidence for multiple regulatory mechanisms controlling PRLR isoform expression in mice. Biology of reproduction 28 18596217
2019 Association of prolactin receptor (PRLR) variants with prolactinomas. Human molecular genetics 27 30445560
1998 Differential expression of prolactin receptor (PRLR) in normal and tumorous adrenal tissues: separation of cellular endocrine compartments by laser capture microdissection (LCM). Endocrine research 26 9888587
2013 Characterization of the novel duplicated PRLR gene at the late-feathering K locus in Lohmann chickens. Journal of molecular endocrinology 25 23940279
2011 DGAT1, GH, GHR, PRL and PRLR polymorphism in water buffalo (Bubalus bubalis). Reproduction in domestic animals = Zuchthygiene 25 21883511
2005 Effect of the polymorphism of prolactin receptor (PRLR) and leptin (LEP) genes on litter size in Polish pigs. Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 24 16274424
2016 Targeting Prolactin Receptor (PRLR) Signaling in PRLR-Positive Breast and Prostate Cancer. The oncologist 23 27107001
2023 Astragalus polysaccharide promotes autophagy and alleviates diabetic nephropathy by targeting the lncRNA Gm41268/PRLR pathway. Renal failure 22 37994436
2017 Preclinical Activity of the Novel Anti-Prolactin Receptor (PRLR) Antibody-Drug Conjugate REGN2878-DM1 in PRLR-Positive Breast Cancers. Molecular cancer therapeutics 21 28377489
2013 Combined effects of four SNPs within goat PRLR gene on milk production traits. Gene 21 23954220
2011 HMGN2 inducibly binds a novel transactivation domain in nuclear PRLr to coordinate Stat5a-mediated transcription. Molecular endocrinology (Baltimore, Md.) 21 21816901
2010 Single nucleotide polymorphisms of the prolactin receptor (PRLR) gene and its association with growth traits in Chinese cattle. Molecular biology reports 21 20349144
2010 Novel SNPs of the bovine PRLR gene associated with milk production traits. Biochemical genetics 21 21165768
1998 Developmental expression and localization of the prolactin receptor (PRL-R) gene in ewe mammary gland during pregnancy and lactation: estimation of the ratio of the two forms of PRL-R messenger ribonucleic acid. Biology of reproduction 21 9603266
2018 Remarkable genetic diversity detected at river buffalo prolactin receptor (PRLR) gene and association studies with milk fatty acid composition. Animal genetics 20 29569734
2022 Energy deprivation-induced AMPK activation inhibits milk synthesis by targeting PrlR and PGC-1α. Cell communication and signaling : CCS 19 35248054
2011 Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk: results from a population-based case-control study in Poland. Breast cancer research : BCR 19 21470416
2017 Natural and molecular history of prolactinoma: insights from a Prlr-/- mouse model. Oncotarget 18 29464061
2011 Molecular characterization, mRNA expression of prolactin receptor (PRLR) gene during pregnancy, nonpregnancy in the yak (Bos grunniens). General and comparative endocrinology 18 22197210
2023 A novel LncRNA SPIRE1/miR-181a-5p/PRLR axis in mandibular bone marrow-derived mesenchymal stem cells regulates the Th17/Treg immune balance through the JAK/STAT3 pathway in periodontitis. Aging 16 37490712
2000 Increase in prolactin receptor (PRL-R) mRNA level in the mammary gland after hormonal induction of lactation in virgin ewes. Domestic animal endocrinology 16 10701763
2016 GHR/PRLR Heteromultimer Is Composed of GHR Homodimers and PRLR Homodimers. Molecular endocrinology (Baltimore, Md.) 15 27003442
2012 The two-component system PrlS/PrlR of Brucella melitensis is required for persistence in mice and appears to respond to ionic strength. Microbiology (Reading, England) 15 22859617
2009 Divergent evolution in the cytoplasmic domains of PRLR and GHR genes in Artiodactyla. BMC evolutionary biology 14 19622175
2024 The immunotoxin targeting PRLR increases tamoxifen sensitivity and enhances the efficacy of chemotherapy in breast cancer. Journal of experimental & clinical cancer research : CR 13 38898487
2019 Molecular characterization and an 80-bp indel polymorphism within the prolactin receptor (PRLR) gene and its associations with chicken growth and carcass traits. 3 Biotech 13 31321200
2014 Polymorphisms of PRLR and FOLR1 genes and association with milk production traits in goats. Genetics and molecular research : GMR 13 24615071
2010 Evaluation of prolactin receptor (PRLR) as candidate gene for male fertility in Hanoverian warmblood horses. Reproduction in domestic animals = Zuchthygiene 13 19845882
2024 Consequences of gene editing of PRLR on thermotolerance, growth, and male reproduction in cattle. FASEB bioAdvances 12 39114445
2019 Two indel variants of prolactin receptor (PRLR) gene are associated with growth traits in goat. Animal biotechnology 12 30987502
2019 miR-142-3p Regulates Milk Synthesis and Structure of Murine Mammary Glands via PRLR-Mediated Multiple Signaling Pathways. Journal of agricultural and food chemistry 12 31369265
2019 Polymorphisms and genetic effects of PRLR, MOGAT1, MINPP1 and CHUK genes on milk fatty acid traits in Chinese Holstein. BMC genetics 12 31419940
2022 Association of PRLR, IGF1, and LEP genes polymorphism with milk production and litter size in Egyptian Zaraibi goat. Tropical animal health and production 11 36155857
2020 Cloning and molecular characterization of PRL and PRLR from turbot (Scophthalmus maximus) and their expressions in response to short-term and long-term low salt stress. Fish physiology and biochemistry 11 31970604
2017 Internal image anti-idiotypic antibody: A new strategy for the development a new category of prolactin receptor (PRLR) antagonist. Molecular immunology 11 28412548
2023 PRL-R Variants Are Not Only Associated With Prolactinomas But Also With Dopamine Agonist Resistance. The Journal of clinical endocrinology and metabolism 10 36638053
2023 High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by L-PRLR and S-PRLR. International journal of molecular sciences 10 37833858
2021 Polymorphisms of the PRLR Gene and Their Association with Milk Production Traits in Egyptian Buffaloes. Animals : an open access journal from MDPI 10 33923003
2021 ABBV-176, a PRLR antibody drug conjugate with a potent DNA-damaging PBD cytotoxin and enhanced activity with PARP inhibition. BMC cancer 10 34107902
2021 Inheritance of the SLICK1 allele of PRLR in cattle. Animal genetics 10 34642995
2014 Two missense mutations in exon 9 of caprine PRLR gene were associated with litter size. Animal genetics 10 25303214
2023 The prolactin receptor gene (PRLR) is linked and associated with the risk of polycystic ovarian syndrome. Journal of ovarian research 8 37993904
2021 Characterization of prolactin (PRL) and PRL receptor (PRLR) in Chinese soft-shelled turtle: Molecular identification, ligand-receptor interaction and tissue distribution. General and comparative endocrinology 8 34715089
2020 Association Analysis between SPP1, POFUT1 and PRLR Gene Variation and Milk Yield, Composition and Coagulation Traits in Sarda Sheep. Animals : an open access journal from MDPI 8 32708940
2020 Immunohistochemical localization of prolactin receptor (PRLR) to Hodgkin's and Reed-Sternberg cells of Hodgkin's lymphoma. Acta histochemica 8 33259941
2000 Cloning and sequence analysis of the extracellular region of the polar bear (Ursus maritimus) luteinizing hormone receptor (LHr), follicle stimulating hormone receptor (FSHr), and prolactin receptor (PRLr) genes and their expression in the testis of the black bear (Ursus americanus). Molecular reproduction and development 8 10618652
1989 Modulation of prolactin receptors (PRL-R) by lactogenic and steroid hormones in human breast cancer cells in long-term tissue culture (T-47D). Anticancer research 8 2764510
2022 The Circ-CYP24A1-miR-224-PRLR Axis Impairs Cell Proliferation and Apoptosis in Recurrent Miscarriage. Frontiers in physiology 7 35309064
2020 Epigenetic modifications in the GH-dependent Prlr, Hnf6, Cyp7b1, Adh1 and Cyp2a4 genes. Journal of molecular endocrinology 7 31990658
2020 Expression and analysis of ESR1, IGF-1, FSH, VLDLR, LRP, LH, PRLR genes in Pekin duck and Black Muscovy duck. Gene 7 33007371
2023 Differential Expression in Endometriosis Tissue versus Endometrium of the Uterine Adenogenesis Factors PRL-R, GH, IGF1, and IGF2. Critical reviews in eukaryotic gene expression 6 37017668
2015 Identification of SNPs within the PRLR gene and effects on maternal behavior in sheep. Genetics and molecular research : GMR 6 26782398
2022 PRL/PRLR Can Promote Insulin Resistance by Activating the JAK2/STAT5 Signaling Pathway. Computational and mathematical methods in medicine 5 36238467
2021 Bu-Shen-Zhu-Yun decoction induces PRLR deubiquitination and JAK2/STAT5 activation via CSN5 in vitro. Aging 5 34424219
2021 Different expression of LHR, PRLR, GH and IGF1 during testicular development of yak. Reproduction in domestic animals = Zuchthygiene 5 34752661
2014 A recent L1 insertion within SPEF2 gene is associated with changes in PRLR expression in sow reproductive organs. Animal genetics 5 24712415
2014 [Associations of PRLR/AluI gene polymorphism with reproductive, growth and meat quality traits in pigs]. TSitologiia i genetika 5 25318178
2011 Characterization of PRLR and PPARGC1A genes in buffalo (Bubalus bubalis). Genetics and molecular biology 5 22215963
2023 Effects of Osmotic Stress on the mRNA Expression of prl, prlr, gr, gh, and ghr in the Pituitary and Osmoregulatory Organs of Black Porgy, Acanthopagrus schlegelii. International journal of molecular sciences 4 36982391
2021 Molecular evolutionary insights from PRLR in mammals. General and comparative endocrinology 4 33872604
2021 The effect of circadian rhythm on prolactin/PRLR-mediated intracellular signaling profiles in vivo and in vitro. Tissue & cell 4 34343759
2019 Cloning and expression analysis of PRL and PRLR genes in black Muscovy duck. British poultry science 4 31630540
2016 Changes in the Expression of the Prolactin Receptor (PRLR) Gene in Different Physiological Stages in the Mammary Gland of the Iranian Adani Goat. Reproduction in domestic animals = Zuchthygiene 4 27333814
2015 Effect of Prolactin Receptor (PRLR) and Beta-Casein (CSN2) Gene Polymorphism on the Chemical Composition of Milk Sows. Folia biologica 4 26255464
1996 Modification of prolactin receptor (PRL-R) expression by PRL in the mouse liver: estimation of the ratio of two forms of PRL-R mRNAs by "one-sided competitive PCR". Zoological science 4 8987522
2023 A novel signaling transduction pathway of melatonin on lactose synthesis in cows via melatonin receptor 1 (MT1) and prolactin receptor (PRLR). PeerJ 3 37692118
2016 Development of a new anti-prolactin receptor (PRLR) antibody, F56, which can serve as a PRLR antagonist. International journal of biological macromolecules 3 27829125
2015 Different intracellular signalling pathways triggered by an anti-prolactin receptor (PRLR) antibody: Implication for a signal-specific PRLR agonist. International journal of biological macromolecules 3 26526176
2009 [Relationship of genetic polymorphism of PRLR and RBP4 genes with litter size traits in pig]. Yi chuan = Hereditas 3 19138903
2000 [Expression of oncogenes (c-myc-neu) and prolactin receptor (PRLr) in tissues of women with endometriosis]. Ginecologia y obstetricia de Mexico 3 10808613
2025 Association of Genes TRH, PRL and PRLR with Milk Performance, Reproductive Traits and Heat Stress Response in Dairy Cattle. International journal of molecular sciences 2 40076589
2023 The Role of PRLR Gene Polymorphisms in Milk Production in European Wild Rabbit (Oryctolagus cuniculus). Animals : an open access journal from MDPI 2 36830458
2023 Retracted: PRL/PRLR Can Promote Insulin Resistance by Activating the JAK2/STAT5 Signaling Pathway. Computational and mathematical methods in medicine 2 38077883
2022 4SC-202 exerts an anti-tumor effect in cervical cancer by targeting PRLR signaling pathway. Journal of molecular histology 2 36272045
2025 Exercise ameliorates hepatic lipid accumulation via upregulating serum PRL and activating hepatic PRLR-mediated JAK2/STAT5 signaling pathway in NAFLD mice. Frontiers in pharmacology 1 40894210
2024 Aloperine Inhibits ASFV via Regulating PRLR/JAK2 Signaling Pathway In Vitro. International journal of molecular sciences 1 39201769
2024 The goat PRLR gene: mRNA expression, association analysis of InDel variants with body weight and growth traits. Gene 1 39522661
2021 MICA-G129R: A bifunctional fusion protein increases PRLR-positive breast cancer cell death in co-culture with natural killer cells. PloS one 1 34077462
2010 [The correlation between the expression of PRL-R and ER/PR in breast cancer]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 20335148
2007 [Preliminary study on the relationship between sow maternal behaviour during early lactation and polymorphism of PRLR gene]. Yi chuan = Hereditas 1 17284423
2025 Osthole suppresses prostate cancer progression by modulating PRLR and the JAK2/STAT3 signaling axis. Frontiers in oncology 0 40978029
2024 The TCONS_00046732/chi-miR-135b-5p/PRLR regulatory axis promotes endometrial epithelial cells growth through the PI3K-Akt signaling pathway. International journal of biological macromolecules 0 39505183

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