Function
The prolactin receptor (PRLR) binds to the anterior pituitary hormone prolactin (PRL). It acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation. This inhibition is achieved through suppression of SRC kinase activation and stimulation of AKT. Isoform 4 of the PRLR lacks the ability to transduce prolactin signaling, as does Isoform 6.
Gene References Into Functions
- A replication study investigating the association between the prolactin receptor gene intron C/T polymorphism (rs37389) and recurrent miscarriage found no association. PMID: 28980840
- Low PRLR expression has been linked to Triple Negative Breast Cancer. PMID: 27480353
- Research indicates promising antitumor activity against PRLR-positive breast cancer xenografts, supporting the evaluation of anti-PRLR antibody-drug conjugates as potential therapeutic agents for breast cancer. PMID: 28377489
- The Prl receptor is expressed at varying levels in most glioblastoma multiforme tumors. Prolactin stimulation leads to increased STAT5 phosphorylation and enhanced cellular invasion. PMID: 27788487
- The PRLRI146L and PRLRI176V variants are not associated with the risk of breast cancer or multiple breast fibroadenomas. PMID: 27575941
- This study identified 4 PRLR variations (p.Ile76Val, p.Ile146Leu, p.Glu108Lys and p.Glu554Gln) in 16 Sporadic Prolactinomas in Humans. PMID: 26641246
- Findings highlight PRLR as an independent predictor of favorable prognosis in human breast cancer. PMID: 26317306
- Two markers for the PRL peptide gene and three markers for the prolactin receptor (PRLR) gene were genotyped. PMID: 26513615
- The prolactin receptor is constitutively expressed on regulatory T and effector T cells in patients with systemic lupus erythematosus, and this expression is higher than in healthy individuals. PMID: 26844452
- There is a potential role for PRLR in the progression of cervical cancer. PMID: 24990775
- Studies demonstrate that position 146 plays a critical role in directing intrinsic properties of the PRLR, including extracellular domain folding, PRL-responsiveness, and ligand-independent activity of the receptor. PMID: 25524456
- Data indicate that cell membrane/lipid bilayer binding of PRLR and tyrosine phosphorylation of PRLR intracellular domain are independent processes. PMID: 25846210
- The long PRLR plays a significant role in breast cancer metastasis. PMID: 26095602
- A residue quartet in the extracellular membrane proximal domain of the homodimeric cytokine receptor prolactin receptor is a key regulator of intracellular signaling discrimination. PMID: 25784554
- PRL induces transient signaling pathways in neurons and modulates ion channels. [review] PMID: 24758841
- Exposure to prolactin increases TNF-alpha release from CD14(+) monocytes of rheumatoid arthritis patients. This can be abolished by PRLR gene silencing or treatment with a MAPK inhibitor. PMID: 24997655
- High MFAB expression is associated with testicular germ cell tumor and glioblastomas. PMID: 24391856
- Negative/low expression is associated with poorly differentiated and larger breast tumors in Poland. PMID: 24249584
- Major changes in prolactin receptor conformation and dimerization affinity are triggered by single mutations in critical regions of D1. PMID: 24735798
- PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. PMID: 24333596
- Hypertrimethylation on H3K27 of the p53 gene promoter region due to elevated expression of DeltaS2 PRLR by alternative splicing of the pre-mRNA in its full-length form might serve as a novel mechanism underlying prostate cancer. PMID: 24032713
- Data suggest that signal transduction via prolactin and the prolactin receptor plays a role in trophoblast cell migration and invasion; PRLR is expressed by extravillous cytotrophoblasts and first-trimester placental bed tissue. PMID: 23849393
- PRL-induced transient signaling in sensory neurons is governed by PI3K or PKCepsilon, mediated via the PRLR-S isoform, and transient effects mediated by PRLR-S are inhibited by the presence of PRLR-L in these cells. PMID: 24142695
- Single nucleotide polymorphisms (SNPs) of the PRLR gene 5' UTR and promoter region are associated with an increased risk for gestational diabetes in a population of Chilean subjects. PMID: 23651351
- Familial hyperprolactinemia appears to be caused by a germline, loss-of-function mutation in PRLR, resulting in prolactin insensitivity. PMID: 24195502
- Results demonstrate a novel function for hepatic PRLR in the regulation of insulin sensitivity and provide important insights into the nutritional regulation of PRLR expression. PMID: 23775766
- Our data suggest that the presence of the prolactin receptor significantly affects growth hormone receptor utilization in breast cancer cells. PMID: 23192981
- The prolactin receptor transactivation domain is associated with steroid hormone receptor expression and malignant progression of breast cancer. PMID: 23159947
- Our findings indicate no significant association of prolactin and PRLR polymorphisms with clozapine response, tardive dyskinesia diagnosis, or its severity in patients with schizophrenia. PMID: 21305610
- The prolactin receptor can be activated by three sequence-diverse human hormones: prolactin, growth hormone, and placental lactogen. [review] PMID: 22577091
- PRLr isoforms expression and PRLr subcellular localization are altered in parathyroid tumors. PMID: 22606260
- The structure of the human prolactin receptor reveals a structural link between the WSXWS motif, hormone binding, and receptor dimerization. We propose this as a general mechanism for class 1 receptor activation. PMID: 22325776
- PRL signaling through the long form prolactin receptor causes reduced fatty acid oxidation, increased lipid storage, glucose intolerance, and obesity. PMID: 21989556
- Data provide limited support for an association between common variations in PRLR and breast cancer risk. PMID: 21470416
- The association of the PRLr with HMGN2 enables Stat5a-responsive promoter binding, thus facilitating transcriptional activation and promoting anchorage-independent growth. PMID: 21816901
- Our study suggests that the prolactin receptor gene is a molecular target that may be important in the pathogenesis and progression of lobular neoplasia. PMID: 20658264
- Enhanced complex formation of ERalpha dimer with SP1 and C/EBPbeta by E2 has an essential role in the transcriptional activation of the hPRLR gene. PMID: 21670145
- Data show that cells expressing higher long:short PRLR ratios had increased growth, survival, and migration in response to PRL. These findings suggest that PRLR antagonists may be therapeutically beneficial in ovarian cancer. PMID: 21775057
- Endogenous growth hormone receptor (GHR) and PRLR associate, possibly as a GHR-PRLR heterodimer, in human breast cancer cells. GH signaling in these cells is largely mediated by the PRLR in the context of both PRLR-PRLR homodimers and GHR-PRLR heterodimers. PMID: 21310852
- Positive correlations in positivity rate between the PRL-R and ER/PR expressions are found only in CerbB-2 positive patients with breast cancer. PMID: 20335148
- SIRPalpha modulates PRL receptor-associated signaling as a function of integrin occupancy by mediating integrin-PRL receptor cross-talk and contributing to breast cancer biology. PMID: 20826546
- Both Zn(2+) and human PRLr binding influence human PRL conformers in an interdependent manner. PMID: 21510945
- Functional impact of manipulation on the relative orientation of human prolactin receptor domains. PMID: 21591677
- Progesterone induces expression of the prolactin receptor gene through cooperative action of Sp1 and C/EBP transcription factors. PMID: 21238538
- Rabbit antibodies have high titers and could specifically recognize each isoform of PRLR in breast cancer cell lines and human breast carcinoma biopsies. PMID: 21144038
- Prolactin receptor signaling contributes to the local inflammatory response within the atherosclerotic plaque and thus to atherogenesis. PMID: 21068074
- Blockade of the PRLR represents a novel treatment approach for patients with advanced breast or prostate cancer with limited therapeutic options. PMID: 20846877
- Acetylation and deacetylation provide a rheostat-like regulation for the cytokine receptor PRLR in its cytoplasmic loop dimerization and subsequent STAT5 activation. PMID: 20962278
- This study visualized for the first time the loop L5 spanning PRLR2 residues Thr133-Phe140, revealing its central implication for the three intermolecular interfaces of the 1:2 complex between natural prolactin and two PRLR chains. PMID: 20875426
- Prolactin receptor expression is common in colorectal cancer. PMID: 20453834
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Involvement In Disease
Multiple fibroadenomas of the breast (MFAB); Hyperprolactinemia (HPRL)
Protein Families
Type I cytokine receptor family, Type 1 subfamily
Subcellular Location
Membrane; Single-pass type I membrane protein.; [Isoform 7]: Secreted.
Tissue Specificity
Expressed in breast, placenta, kidney, liver and pancreas.