Biotinylated Prolactin R/PRLR His&Avi Tag Protein, Human

The prolactin receptor (PRLR) belongs to the type I cytokine receptor superfamily and is expressed as a homodimer on mammary epithelial, hepatic, pancreatic, and hematopoietic cells. Structurally, its extracellular region consists of two fibronectin type III domains and a WSXWS motif, while the stem domain mediates ligand-induced receptor dimerization; the intracellular tail contains Box1/Box2 motifs that recruit JAK2 upon activation. Prolactin binding triggers conformational rearrangement, initiating the JAK2-STAT5, MAPK, and PI3K signaling pathways to govern mammary gland development, lactation initiation and maintenance, systemic metabolic homeostasis, and reproductive endocrine function. PRLR signaling carries significant clinical implications in oncology and endocrinology: prospective epidemiological studies demonstrate that elevated plasma prolactin concentrations are associated with increased risk of postmenopausal breast cancer, particularly hormone receptor-positive subtypes; conversely, acidosis within the tumor microenvironment selectively abrogates PRLR-mediated STAT5 phosphorylation, thereby disrupting the hormone's anti-invasive effects and facilitating malignant progression. Germline loss-of-function mutations in PRLR, exemplified by the His188Arg variant, result in familial hyperprolactinemia characterized by oligomenorrhea and infertility due to impaired JAK2-STAT5 signaling. Additionally, the PRLR short isoform functions as a tumor suppressor in pancreatic ductal adenocarcinoma by engaging the NEK9-Hippo axis to downregulate pentose phosphate pathway enzymes and restrain nucleotide biosynthesis. These multifaceted biological roles have positioned PRLR as an attractive therapeutic target, with clinical-stage interventions including the monoclonal antibody antagonist LFA102 and the antibody-drug conjugate ABBV-176 being evaluated in solid tumor trials.