Affinage

PRLR

Prolactin receptor · UniProt P16471

Round 2 corrected
Length
622 aa
Mass
69.5 kDa
Annotated
2026-04-28
130 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRLR is a transmembrane cytokine receptor that transduces prolactin signaling to control lactation, reproduction, metabolism, and cell proliferation through JAK2-dependent activation of STAT5, STAT3, AKT, and ERK pathways. PRLR pre-dimerizes in a ligand-independent manner, and prolactin binding induces a conformational change—facilitated by cyclophilin A—that activates JAK2; the ratio of long to short receptor isoforms modulates signaling output, with the short isoform capable of engaging non-canonical pathways such as NEK9–Hippo–TEAD1 to suppress the pentose phosphate pathway in pancreatic cancer (PMID:19535262, PMID:9603266, PMID:33664869). In addition to canonical membrane signaling, nuclear PRLR functions as a transcriptional coactivator by recruiting HMGN2 to enable STAT5a promoter occupancy, and receptor protein stability is controlled by β-TrCP-mediated ubiquitination/lysosomal degradation opposed by CSN5-mediated deubiquitination (PMID:21816901, PMID:35248054, PMID:34424219). Ovarian PRLR is required for luteal progesterone production essential for embryo implantation, and hepatic PRLR regulates insulin sensitivity through STAT5, while a gain-of-function intracellular variant (Asn492Ile) selectively enhances PI3K-AKT signaling and is associated with prolactinomas (PMID:10803598, PMID:23775766, PMID:30445560).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1989 Medium

    Establishing that PRLR expression is hormonally regulated—progestins upregulate PRLR in breast cancer cells while lactogenic hormones cause downregulation—defined the receptor as a dynamically controlled signaling node rather than a constitutive surface marker.

    Evidence Radioligand binding assays in T-47D cells with steroid and hormone treatments

    PMID:2764510

    Open questions at the time
    • Mechanism of progestin-induced transcriptional upregulation not defined
    • No in vivo validation of progestin regulation
  2. 1992 Medium

    Detection of both long and short PRLR isoforms in hypothalamus, pituitary, and liver established that the same receptor variants mediating peripheral actions also operate at central feedback sites, raising the question of isoform-specific function.

    Evidence RT-PCR with isoform-specific primers in rat tissues

    PMID:1537321

    Open questions at the time
    • No functional distinction between isoforms established
    • Protein-level confirmation not provided
  3. 1998 Medium

    Correlation of long-to-short PRLR isoform ratio with lactogenesis onset in the mammary gland suggested that isoform balance controls differentiation signaling magnitude, with the short form acting as a dominant negative.

    Evidence RNase protection assay and in situ hybridization across pregnancy/lactation in ewe mammary gland

    PMID:9603266

    Open questions at the time
    • Dominant-negative activity of short isoform not directly demonstrated
    • Mechanism of isoform switching not identified
  4. 2000 High

    Genetic loss-of-function resolved that PRLR's role in implantation is mediated through ovarian luteal progesterone production rather than direct uterine action, as progesterone rescue fully restored implantation in PRLR-knockout mice.

    Evidence PRLR−/− mice with exogenous progesterone rescue; gene expression analysis of implantation markers

    PMID:10803598

    Open questions at the time
    • Downstream signaling pathway in corpus luteum not dissected
    • Whether PRLR has any direct uterine function beyond implantation remains unresolved
  5. 2009 Medium

    The discovery that PRLR pre-dimerizes without ligand and that prolactin binding induces a conformational change (with cyclophilin A participation) to activate JAK2 overturned the simple ligand-induced dimerization model and established a conformational activation mechanism.

    Evidence Biochemical and cell-based assays of pre-dimerization and cyclophilin A involvement (reviewed from Clevenger lab data)

    PMID:19535262

    Open questions at the time
    • Structural basis of pre-dimer conformational transition not resolved at atomic level
    • Cyclophilin A mechanism of action on PRLR not fully defined
  6. 2011 High

    Identification of nuclear PRLR as a transcriptional coactivator that recruits HMGN2 to enable STAT5a promoter binding revealed a non-canonical signaling mode independent of classical membrane-to-nucleus JAK-STAT relay.

    Evidence Co-immunoprecipitation, mutagenesis of transactivation domain, promoter-binding assays, anchorage-independent growth assays

    PMID:21816901

    Open questions at the time
    • Nuclear import mechanism for PRLR not defined
    • Genome-wide targets of nuclear PRLR-HMGN2 complex unknown
    • Relevance in non-transformed cells not established
  7. 2013 High

    Demonstration that hepatic PRLR regulates insulin sensitivity through STAT5, with expression controlled by leucine/GCN2/mTOR/S6K1, linked PRLR to metabolic homeostasis beyond its classical reproductive roles.

    Evidence Adenoviral overexpression and knockdown of PRLR in mice; in vitro insulin sensitivity assays with pathway inhibitors

    PMID:23775766

    Open questions at the time
    • Specific STAT5 target genes mediating insulin sensitization not identified
    • Human relevance of hepatic PRLR-insulin axis not established
  8. 2016 High

    Split-luciferase and Co-IP studies revealed that PRLR and GHR form ligand-independent heteromultimeric assemblages composed of respective homodimers, with ligand binding driving distinct conformational consequences, expanding the model of PRLR signaling to include cross-talk with GHR.

    Evidence Split-luciferase complementation and co-immunoprecipitation in T47D breast cancer cells

    PMID:27003442

    Open questions at the time
    • Functional signaling output of GHR-PRLR heteromultimer not characterized
    • Stoichiometry and structural arrangement of the heteromultimer unknown
  9. 2019 High

    The Asn492Ile variant in the PRLR intracellular domain was shown to selectively enhance PI3K-AKT but not STAT5 signaling, establishing pathway-biased gain-of-function as a mechanism for prolactinoma pathogenesis.

    Evidence In vitro expression of PRLR variants with Western blot for pAkt/pSTAT5, proliferation assays, and pharmacological Akt inhibition rescue

    PMID:30445560

    Open questions at the time
    • Structural basis for pathway-selective gain-of-function unknown
    • Penetrance and frequency of Asn492Ile in prolactinoma patients not fully determined
  10. 2021 High

    The short PRLR isoform was found to suppress the pentose phosphate pathway in pancreatic cancer through a NEK9–Hippo–TEAD1 signaling axis, identifying a non-canonical tumor-suppressive metabolic function for a specific PRLR isoform.

    Evidence Co-IP, proximity ligation assay, ChIP, 13C metabolite tracing, and xenograft models

    PMID:33664869

    Open questions at the time
    • How NEK9 discriminates between short and long PRLR isoforms mechanistically unknown
    • Relevance to other cancer types not tested
  11. 2022 High

    Identification of β-TrCP as the E3 ubiquitin ligase for PRLR, triggered by AMPK activation and leading to lysosomal degradation, established the first complete ubiquitin-dependent degradation pathway for the receptor; this was complemented by discovery of CSN5 as the opposing deubiquitinase.

    Evidence In vitro ubiquitination assays, β-TrCP knockdown/overexpression, AMPK activator/inhibitor treatments (for β-TrCP); Co-IP, shRNA knockdown of CSN5, promoter assays (for CSN5)

    PMID:34424219 PMID:35248054

    Open questions at the time
    • Specific ubiquitination sites on PRLR not mapped
    • Whether β-TrCP and CSN5 act on the same ubiquitin chains not determined
    • Physiological conditions switching between degradation and stabilization not fully defined
  12. 2024 Medium

    CRISPR-mediated introduction of PRLR C-terminal truncation mutations (mimicking natural slick-hair variants) into cattle confirmed that the intracellular signaling domain controls thermoregulation and growth without deleterious reproductive effects, providing in vivo causal evidence for domain-specific PRLR function.

    Evidence CRISPR/Cas9 gene editing in Angus and Jersey cattle with phenotypic assessment of thermoregulation, growth, and reproduction

    PMID:39114445

    Open questions at the time
    • Molecular mechanism linking PRLR truncation to hair follicle and thermoregulatory phenotype unknown
    • Whether truncated PRLR retains partial JAK2/STAT5 signaling in bovine skin not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of PRLR pre-dimer conformational activation, the genome-wide target repertoire of nuclear PRLR-HMGN2 complexes, the precise ubiquitination sites controlling receptor turnover, and how isoform-specific signaling is achieved at the molecular level.
  • No high-resolution structure of full-length PRLR in pre-dimer or activated conformation
  • Nuclear PRLR coactivator function not validated by genome-wide approaches (ChIP-seq)
  • Isoform-specific interactome not systematically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 2 GO:0005764 lysosome 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 2 R-HSA-1430728 Metabolism 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-1474165 Reproduction 1 R-HSA-168256 Immune System 1
Partners
BTRCCOPS5CYPAGHRHMGN2JAK2NEK9STAT5A
Complex memberships
GHR-PRLR heteromultimerPRLR homodimerPRLR-HMGN2 nuclear complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PRL receptor (PRL-R) localizes to the nucleus in hypothalamic dopaminergic neurons (in addition to membrane and cytoplasm), as detected by immunocytochemistry with antibodies against the extracellular and ligand-binding domains; the ligand-binding domain of PRL-R may be involved in trafficking PRL in the median eminence via tanycyte processes. Double-label confocal immunocytochemistry with domain-specific antibodies (extracellular vs. ligand-binding domain) Brain research Medium 9748546
1992 Both long and short isoforms of PRL-R mRNA are expressed in the rat hypothalamus and anterior/posterior pituitary gland, as well as in liver, but not in cerebral cortex or skeletal muscle, supporting a role for PRL feedback at these central sites through the same receptor isoforms that mediate peripheral actions. RT-PCR with isoform-specific primers from rat brain and pituitary tissue Endocrinology Medium 1537321
2009 PRLr pre-dimerizes in the absence of ligand, and ligand-induced conformational change of the PRLr complex (rather than simple dimerization) is necessary for activation of JAK2; the prolyl isomerase cyclophilin A participates in ligand-induced activation of PRLr-associated JAK2 kinase. Biochemical and cell-based assays reviewed; cyclophilin A interaction and conformational change mechanism described Trends in endocrinology and metabolism: TEM Medium 19535262
2000 Implantation and decidualization defects in PRLR-deficient mice are mediated by failure of ovarian (luteal) PRLR signaling to produce sufficient progesterone, not by absence of uterine PRLR; progesterone administration rescues implantation and restores expression of implantation-specific genes (LIF, COX-2, VEGF, etc.) in PRLR-/- mice. Genetic rescue experiment in PRLR-/- mice with exogenous progesterone; gene expression analysis of implantation markers Endocrinology High 10803598
2013 Hepatic PRLR regulates insulin sensitivity via the STAT5 signaling pathway; adenoviral overexpression of PRLR improves insulin sensitivity while knockdown impairs it; STAT5 activation is required for this effect. PRLR expression is regulated by leucine availability through a GCN2/mTOR/S6K1-dependent pathway. Adenoviral overexpression and knockdown of PRLR in mice; in vitro insulin sensitivity assays; pathway blockade experiments Diabetes High 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 the intermediator between PRLR-SF and the Hippo pathway; TEAD1 (downstream of Hippo/YAP) directly regulates expression of PPP rate-limiting enzymes G6PD and TKT. Co-immunoprecipitation, proximity ligation assay, chromatin immunoprecipitation, promoter luciferase, 13C-labeled metabolite tracing, xenograft models Theranostics High 33664869
2019 PRLR silencing in hippocampal CA3 neurons inhibits the JAK2-STAT5 signaling pathway, reduces apoptosis (decreased Caspase-3 and Bax, increased Bcl-2), and increases BDNF expression in a chronic mild stress mouse model of depression. Lentiviral shRNA knockdown/overexpression of PRLR in mice; Western blot, immunohistochemistry, serum BDNF measurement Brain research Medium 31545956
2019 PRLR variant Asn492Ile in the intracellular domain increases prolactin-induced pAkt signaling (>1.3-fold) and cell proliferation (1.4-fold) compared to wild-type PRLR without affecting pSTAT5 signaling; Akt pathway inhibition (Akt1/2 inhibitor or everolimus) reduces Asn492Ile-driven signaling and proliferation to wild-type levels, demonstrating a gain-of-function mutation in PI3K-Akt signaling. In vitro expression of PRLR variants; Western blot for pAkt and pSTAT5; cell proliferation assays; pharmacological inhibition of Akt pathway Human molecular genetics High 30445560
2011 Nuclear PRLR functions as a transcriptional coactivator through a novel transactivation domain that is activated by ligand-induced phosphorylation; phosphorylated nuclear PRLR recruits HMGN2 (high-mobility group N2 protein), and this PRLr-HMGN2 complex enables STAT5a binding to target promoters to drive transcriptional activation and anchorage-independent growth. Co-immunoprecipitation, promoter-binding assays, mutagenesis of transactivation domain, phosphorylation analysis, anchorage-independent growth assays Molecular endocrinology High 21816901
1998 In the ewe mammary gland, the ratio of long to short form of PRL-R mRNA increases during lactogenesis and correlates with activation of milk protein gene transcription; the short form may act as a dominant negative to suppress differentiation-related signaling. RNase protection assay, Northern blot, in situ hybridization across pregnancy and lactation time points Biology of reproduction Medium 9603266
2016 GHR and PRLR form heteromultimeric assemblages in breast cancer cells; split-luciferase complementation and Co-IP demonstrate that PRLR-PRLR and GHR-PRLR form ligand-independent assemblages, but the GHR/PRLR heteromultimer is composed of GHR homodimers and PRLR homodimers (rather than GHR-PRLR heterodimers); GH or PRL augments PRLR-PRLR complementation while both ligands cause decline in GHR-PRLR heteromer complementation, indicating distinct conformational consequences. Split luciferase complementation assay, co-immunoprecipitation in T47D breast cancer cells Molecular endocrinology High 27003442
2022 AMPK activation triggers ubiquitination of PrlR (prolactin receptor) via the E3 ligase β-TrCP, leading to PrlR degradation through lysosomal endocytosis, which attenuates prolactin signaling and reduces milk protein synthesis; this identifies β-TrCP as a writer for PrlR ubiquitination. In vitro ubiquitination assays, lysosomal inhibitor experiments, β-TrCP knockdown/overexpression, AMPK activator/inhibitor treatments in mammary epithelial cells Cell communication and signaling High 35248054
2008 In mouse fallopian tubes, PRLR long form expression is regulated by PRL itself (decreased by exogenous PRL, increased by bromocriptine-mediated PRL suppression), and independently by progesterone (P4), which selectively suppresses PRLR isoforms; in contrast, P4 does not regulate PRLR in the pituitary, demonstrating tissue-specific regulation of PRLR isoforms by both PRL and ovarian steroids through distinct mechanisms. Western blot for PRLR isoforms, bromocriptine treatment, exogenous hormone administration in prepubertal mice; tissue-specific comparison Biology of reproduction Medium 18596217
2013 The duplicated PRLR (dPRLR) in late-feathering chickens can be potently activated by chicken PRL and functionally couples to the intracellular STAT5 signaling pathway, as demonstrated in HepG2 cells using a STAT5-Luciferase reporter; dPRLR lacks the 149-aa C-terminal tail of full-length PRLR but retains signaling capacity. 5× STAT5-Luciferase reporter system, Western blot in HepG2 cells; 3'-RACE cloning Journal of molecular endocrinology Medium 23940279
2023 In mandibular BM-MSCs, PRLR is a downstream target of miR-181a-5p; PRLR knockdown or miR-181a-5p overexpression activates JAK/STAT3 signaling, disrupting Th17/Treg immune balance; PRLR overexpression in BM-MSCs enhances immunosuppressive properties in a periodontitis mouse model, placing PRLR as a positive regulator of immunosuppression via suppression of JAK/STAT3 in mesenchymal stem cells. Luciferase reporter assay (miR-181a-5p/PRLR 3'UTR), siRNA knockdown, overexpression, co-culture with CD4 T cells, in vivo periodontitis mouse model Aging Medium 37490712
1989 In T-47D human breast cancer cells, progestins (Org 2058) specifically upregulate PRL-R expression (up to 186% increase), an effect blocked by the antiprogestin RU 486; hGH and hPL cause down-regulation at high concentrations, while ovine PRL has no effect; estradiol, cortisol, and dexamethasone have no effect on PRL-R levels, establishing progestin-dependent and homologous regulation of PRL-R. Radioligand binding assay on total cell membranes; pharmacological modulation with various steroids and lactogenic hormones in long-term cell culture Anticancer research Medium 2764510
2021 In Chinese soft-shelled turtle, the membrane-proximal ligand-binding domain (not the membrane-distal domain) of PRLR is the critical domain for PRL binding and activation of JAK2-STAT5 signaling, demonstrated using a PRLR mutant (PRLR-M2) lacking the membrane-distal ligand-binding domain that retains dose-dependent PRL-activated STAT5 luciferase reporter activity. 5× STAT5-Luciferase reporter system with domain-deletion mutants; recombinant PRL protein from E. coli General and comparative endocrinology Medium 34715089
2021 High prolactin concentration induces apoptosis in ovine ovarian granulosa cells by downregulating both long (L-PRLR) and short (S-PRLR) isoforms of PRLR, which activates oxidative stress (elevated ROS, decreased mitochondrial respiratory chain complex activity, decreased T-AOC and SOD) and autophagic pathways; knockdown of either L-PRLR or S-PRLR reduces mitochondrial function while overexpression has the opposite effect. Knockdown/overexpression of L-PRLR and S-PRLR in granulosa cells; ROS measurement, mitochondrial respiratory complex activity, glutathione rescue experiments International journal of molecular sciences Medium 37833858
2015 An anti-PRLR monoclonal antibody (B6) that partially overlaps the PRL binding epitope activates distinct intracellular signaling compared to PRL: B6 activates AKT, ERK1/2, STAT1, and STAT3 but not STAT5, whereas PRL activates STAT5; this demonstrates that PRLR can transduce different signaling programs depending on the nature of the activating ligand (signal-specific agonism). Competitive receptor-binding assay, Western blot for signaling molecules (pAKT, pERK1/2, pSTAT1, pSTAT3, pSTAT5) in T-47D and CHO-PRLR cells International journal of biological macromolecules Medium 26526176
2021 Circadian clock dysfunction (Clock-/- mice) significantly downregulates PRL/PRLR-mediated JAK2-STAT5 signaling in vivo and in vitro; the mechanism involves upregulation of SOCS (suppressor of cytokine signaling) negative regulatory molecules in Clock-deficient mammary epithelial cells. Clock-/- mouse model, siRNA knockdown of Clock in mammary epithelial cells, Western blot for JAK2, STAT5 phosphorylation and SOCS levels Tissue & cell Low 34343759
2023 Melatonin suppresses lactose synthesis in cow mammary epithelial cells via a MT1 receptor → PRLR downregulation → SLC35B1 (galactose transporter) suppression pathway; MT1 activation decreases PRLR mRNA expression, which in turn reduces SLC35B1 expression and galactose transport to the Golgi for lactose synthesis. In vivo melatonin feeding, mammary epithelial cell culture, gene expression analysis, pathway dissection PeerJ Low 37692118
2021 Bu-Shen-Zhu-Yun Decoction reverses hyperprolactinemia-induced PRLR ubiquitination and JAK2/STAT5 pathway suppression by increasing CSN5 (COP9 signalosome subunit 5)-mediated deubiquitination of PRLR; GATA1 transcription factor binds the CSN5 promoter to drive CSN5 expression, which deubiquitinates PRLR and restores signaling. Co-immunoprecipitation, renilla luciferase promoter activity, RT-qPCR, Western blot, shRNA knockdown of CSN5 Aging Medium 34424219
2022 PRL/PRLR promotes insulin resistance in adipocytes by activating the JAK2/STAT5 signaling pathway, leading to increased triglyceride deposition; PRLR overexpression in an oleic acid-induced insulin resistance model increases TG content and activates p-JAK2 and p-STAT5. (NOTE: this paper was subsequently retracted - see PMID 38077883) Western blot, TG colorimetry in SW872 adipocytes; PRLR overexpression Computational and mathematical methods in medicine Low 36238467
2024 AMPK-mediated degradation of PrlR is reversed by tamoxifen treatment, which alkalizes lysosomes and causes accumulation of PRLR protein in breast cancer cells; PRL-PRLR axis activation decreases ERα-positive breast cancer cell sensitivity to tamoxifen, and immunotoxin N8-PE24 targeting PRLR restores tamoxifen sensitivity. RNA-seq analysis, exogenous PRL and PRL overexpression cell models, lysosomal alkalinization experiments, 3D spheroid culture, xenograft models Journal of experimental & clinical cancer research Medium 38898487
2025 Exercise elevates serum PRL, which activates hepatic PRLR-mediated JAK2/STAT5 signaling (increased PRLR expression, p-JAK2, and p-STAT5) to reduce intrahepatic lipid accumulation in NAFLD mice; PRLR expression and downstream signaling are reduced in NAFLD mice and restored by exercise intervention. NAFLD mouse model, aerobic exercise intervention, Western blot for PRLR, p-JAK2, p-STAT5, liver histology (HE staining, Oil Red O) Frontiers in pharmacology Low 40894210
2025 Osthole downregulates PRLR expression and decreases phosphorylation of JAK2 and STAT3 in prostate cancer cells, inhibiting cell proliferation and migration in a dose-dependent manner in vitro and reducing tumor volume in vivo. Network pharmacology, CCK-8 proliferation assay, transwell invasion assay, Western blot, molecular docking, xenograft model Frontiers in oncology Low 40978029
2019 miR-142-3p directly targets PRLR mRNA; knockdown of miR-142-3p in mouse mammary gland epithelial cells increases PRLR expression and activates downstream mTOR, SREBP1, cyclin D1, and STAT5 signaling, increasing triglyceride and β-casein synthesis; in vivo knockdown in murine mammary gland increases lobule/duct number and milk production capacity. miR-142-3p knockdown in vitro and in vivo, Western blot for downstream targets, triglyceride measurement, immunofluorescence Journal of agricultural and food chemistry Medium 31369265
2020 Anti-PRLR antibody REGN2878 and its ADC REGN2878-DM1 are rapidly internalized into lysosomes upon binding PRLR, and block PRL-mediated signaling activation in vitro; REGN2878-DM1 induces cell-cycle arrest and cytotoxicity in PRLR-expressing tumor cells and shows additive activity with fulvestrant. In vitro PRLR internalization/trafficking assay, cell-cycle analysis, cytotoxicity assay, xenograft models Molecular cancer therapeutics Medium 28377489
2020 Epigenetic analysis reveals that sex differences in hepatic Prlr gene expression in mice are partly regulated by promoter methylation: lower Prlr promoter methylation in females correlates with higher Prlr mRNA; disruption of GH secretion (neuroDrd2KO mice) reduces methylation and masculinizes Prlr expression, while neonatal androgenization does not affect Prlr methylation. Promoter methylation analysis, qRT-PCR, transgenic/androgenized mouse models Journal of molecular endocrinology Low 31990658
2021 The SLICK1 allele of PRLR, which causes truncation of the C-terminal region involved in JAK2/STAT5 activation, is inherited consistent with Hardy-Weinberg equilibrium in cattle, indicating it does not cause embryonic or fetal lethality; this establishes that JAK2/STAT5-activating C-terminal domain truncation is compatible with survival. Genotyping of 525 Holstein and Senepol cattle from SLICK1 heterozygous matings; chi-square test for HWE Animal genetics Low 34642995
2024 CRISPR/Cas9 introduction of thermotolerance-conferring PRLR mutations (equivalent to natural slick-hair variants causing C-terminal truncation) into Angus and Jersey cattle confers superior thermoregulatory capacity (reduced vaginal/rectal temperature under heat stress) and enhanced growth and scrotal circumference, with no deleterious effects on carcass or reproductive function. CRISPR/Cas9 gene editing, phenotypic assessment of thermoregulation, growth, and reproduction in gene-edited cattle vs. controls FASEB bioAdvances Medium 39114445

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2001 A phosphatase associated with metastasis of colorectal cancer. Science (New York, N.Y.) 558 11598267
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2003 PRL-3 and PRL-1 promote cell migration, invasion, and metastasis. Cancer research 234 12782572
2000 Prenylation-dependent association of protein-tyrosine phosphatases PRL-1, -2, and -3 with the plasma membrane and the early endosome. The Journal of biological chemistry 184 10747914
2003 PRL-3 expression in metastatic cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 177 14654542
1998 Mouse PRL-2 and PRL-3, two potentially prenylated protein tyrosine phosphatases homologous to PRL-1. Biochemical and biophysical research communications 164 9514946
2010 PCBP1 suppresses the translation of metastasis-associated PRL-3 phosphatase. Cancer cell 153 20609352
2004 High expression of PRL-3 promotes cancer cell motility and liver metastasis in human colorectal cancer: a predictive molecular marker of metachronous liver and lung metastases. Clinical cancer research : an official journal of the American Association for Cancer Research 144 15534108
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2004 Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells. The American journal of pathology 142 15161639
2010 High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients. Cancer research 138 21135111
2005 PRL-3 phosphatase is implicated in ovarian cancer growth. Clinical cancer research : an official journal of the American Association for Cancer Research 126 16203771
2001 Role of PRL-3, a human muscle-specific tyrosine phosphatase, in angiotensin-II signaling. Biochemical and biophysical research communications 116 11355880
2002 The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the mitotic spindle and is required for normal mitosis. The Journal of biological chemistry 108 12235145
2002 Pentamidine is an inhibitor of PRL phosphatases with anticancer activity. Molecular cancer therapeutics 107 12516958
2014 Tumor-associated macrophage-derived IL-6 and IL-8 enhance invasive activity of LoVo cells induced by PRL-3 in a KCNN4 channel-dependent manner. BMC cancer 103 24885636
2014 The protein tyrosine phosphatase PRL-2 interacts with the magnesium transporter CNNM3 to promote oncogenesis. Oncogene 100 24632616
2012 Molecular mechanisms of the PRL phosphatases. The FEBS journal 100 22413991
2004 Structural insights into molecular function of the metastasis-associated phosphatase PRL-3. The Journal of biological chemistry 100 14704153
2006 Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer. British journal of cancer 98 16832410
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
2012 miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3. Cancer letters 93 22469786
2007 Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells. Blood 88 17934070
2006 PRL-3 initiates tumor angiogenesis by recruiting endothelial cells in vitro and in vivo. Cancer research 86 17018620
2015 Ubiquitin-Specific Protease 4-Mediated Deubiquitination and Stabilization of PRL-3 Is Required for Potentiating Colorectal Oncogenesis. Cancer research 85 26669864
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 79 18713476
2021 Crosstalk between PRLR and EGFR/HER2 Signaling Pathways in Breast Cancer. Cancers 58 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
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
2014 Prolactin (PRL) and prolactin receptor (PRLR) genes and their role in poultry production traits. Folia biologica 41 24745142
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
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
2020 A novel bispecific antibody targeting CD3 and prolactin receptor (PRLR) against PRLR-expression breast cancer. Journal of experimental & clinical cancer research : CR 39 32398042
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
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
2023 Prolactin receptor signaling: A novel target for cancer treatment - Exploring anti-PRLR signaling strategies. Frontiers in endocrinology 27 36714582
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
2019 Association of prolactin receptor (PRLR) variants with prolactinomas. Human molecular genetics 25 30445560
2013 Characterization of the novel duplicated PRLR gene at the late-feathering K locus in Lohmann chickens. Journal of molecular endocrinology 25 23940279
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
2011 DGAT1, GH, GHR, PRL and PRLR polymorphism in water buffalo (Bubalus bubalis). Reproduction in domestic animals = Zuchthygiene 23 21883511
2023 Astragalus polysaccharide promotes autophagy and alleviates diabetic nephropathy by targeting the lncRNA Gm41268/PRLR pathway. Renal failure 22 37994436
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
2017 Preclinical Activity of the Novel Anti-Prolactin Receptor (PRLR) Antibody-Drug Conjugate REGN2878-DM1 in PRLR-Positive Breast Cancers. Molecular cancer therapeutics 20 28377489
2022 Energy deprivation-induced AMPK activation inhibits milk synthesis by targeting PrlR and PGC-1α. Cell communication and signaling : CCS 19 35248054
2018 Remarkable genetic diversity detected at river buffalo prolactin receptor (PRLR) gene and association studies with milk fatty acid composition. Animal genetics 19 29569734
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
2011 Molecular characterization, mRNA expression of prolactin receptor (PRLR) gene during pregnancy, nonpregnancy in the yak (Bos grunniens). General and comparative endocrinology 18 22197210
2017 Natural and molecular history of prolactinoma: insights from a Prlr-/- mouse model. Oncotarget 17 29464061
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
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 15 37490712
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
2016 GHR/PRLR Heteromultimer Is Composed of GHR Homodimers and PRLR Homodimers. Molecular endocrinology (Baltimore, Md.) 14 27003442
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
2010 Evaluation of prolactin receptor (PRLR) as candidate gene for male fertility in Hanoverian warmblood horses. Reproduction in domestic animals = Zuchthygiene 13 19845882
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
2014 Polymorphisms of PRLR and FOLR1 genes and association with milk production traits in goats. Genetics and molecular research : GMR 12 24615071
2024 Consequences of gene editing of PRLR on thermotolerance, growth, and male reproduction in cattle. FASEB bioAdvances 11 39114445
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
2017 Internal image anti-idiotypic antibody: A new strategy for the development a new category of prolactin receptor (PRLR) antagonist. Molecular immunology 11 28412548
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
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 10 31970604
2014 Two missense mutations in exon 9 of caprine PRLR gene were associated with litter size. Animal genetics 10 25303214
2023 PRL-R Variants Are Not Only Associated With Prolactinomas But Also With Dopamine Agonist Resistance. The Journal of clinical endocrinology and metabolism 9 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 8 37833858
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
2023 The prolactin receptor gene (PRLR) is linked and associated with the risk of polycystic ovarian syndrome. Journal of ovarian research 7 37993904
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 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
2021 Molecular evolutionary insights from PRLR in mammals. General and comparative endocrinology 4 33872604
2021 Bu-Shen-Zhu-Yun decoction induces PRLR deubiquitination and JAK2/STAT5 activation via CSN5 in vitro. Aging 4 34424219
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 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 3 36982391
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
2021 The effect of circadian rhythm on prolactin/PRLR-mediated intracellular signaling profiles in vivo and in vitro. Tissue & cell 3 34343759
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
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
2023 Retracted: PRL/PRLR Can Promote Insulin Resistance by Activating the JAK2/STAT5 Signaling Pathway. Computational and mathematical methods in medicine 1 38077883
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