Prolactin receptor
Prolactin Receptor | |
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Identifiers | |
Symbol | PRLR |
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StructureThe prolactin receptor (PRLR) is a immune cells, as well as adrenal and pituitary glands.
Several PRLR extracellular domains , which are the regions binding to PRLR.
Diversity of PRLR is a result of transcription initiation in different sites of the PRLR promoter region. Additionally, post-translational modifications, like alternative splicing are the events that result in the different isoforms that allow for all the different actions of prolactin in the body.[3]
SignalingThe PRLR is a class 1 cytokine receptor that uses messenger pathways to control second messenger cascades , including:
FunctionExpression of the PRLR protein is found within cells of the mammary glands LigandsAgonists
AntagonistsProlactin receptor antagonists such as Del1-9-G129R-hPRL have been developed.[18][19][20][21][22] Dopamine agonists are currently the most common methods used for treating hyperprolactinemia. However, since dopamine agonists only negatively regulate prolactin production from the pituitary gland, a few studies have tried to develop prolactin receptor antagonists for potentially treating the dopamine-resistant local hyperprolactinemia.[18][23] Δ1–9-G129R-hPRL is one of the prolactin receptor antagonists been studied. Δ1–9-G129R-hPRL as a mutant (inactivated) form of prolactin which exerts its antagonist effect by competing with prolactin to bind with prolactin receptors; thereby, inhibiting the agonist effects of prolactin on prolactin receptors.[18] Besides molecular antagonists, antibodies can also potentially be used to inhibit prolactin receptor signaling. LFA102 is a monoclonal antibody that has been studied and tested for disrupting prolactin receptor's signaling in breast cancers and prostate cancers.[24] Although LFA102 has been proved sufficient to reduce prolactin receptor signaling based on in vitro and in vivo (mouse) studies, LFA102 likely has low effects on limiting tumor growth (breast and prostate cancer) as shown in phase I clinical trials.[24][25] Prolactin receptor dysfunctionPRLR dysfunction has been seen to positively regulate the proliferation of malignant cells in breast cancer. Defects on prolactin receptor signalling can trigger tumour activity, rather than suppress. Signal control is monitored by a variety of genes, and the PRLR gene has been identified in the tissue of metastatic primary breast cancer cells.[26] The defect in the gene is thought to have built a resistance to chemotherapy, and has lost the ability to regulate the apoptosis of cells with mutated DNA.[27] This signalling defect then fails to promote the cellular differentiation, and promotes the upstream survival of the cancerous cells. In breast cancer, the survival of the breast epithelial cells resemble the malignant cells, characteristically known to have an increased proliferative rate.[28]
See alsoReferences
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