User:Izzymuot29/sandbox
Structure[edit]
The prolactin receptor (PRLR) is a membrane-bound protein of the cytokine receptor superfamily. In humans, it is encoded by a single gene which contains 11 exons and is located on chromosome 5. [1] PRLR expression can be found in several tissues such as the gonads, breast, uterus, heart, liver, kidney, brain, immune cells, as well as adrenal and pituitary glands.
Several PRLR isoforms have been described in different tissues. These have varying lengths and cytoplasmic domain composition, but share identical 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. [2]
Signalling[edit]
The PRLR is a class 1 cytokine receptor that uses messenger pathways to control cell proliferation, migration, intracellular ion concentration and inhibit programmed cell death (apoptosis).[3][4] PRLRs also have functions in the second messenger cascades, including:
- JAK-STAT pathway – the STAT protein family has been shown to have a key transduction role in cytokine receptor signalling; this pathway is initiated following the activation of PRLRs.[5] Although there have been 4 STAT proteins identified as transducer molecules of PRLR, STAT5 is recognised as the most important transducer of PRLR isoforms, with a role in inhibiting regulation of gene transcription.
- Ras-Raf-MAPK – initiated by PRLR activation. Phosphotyrosine residues on PRLR act as binding sites for adapter proteins – these connect PRLR to the Ras/Raf/MAP kinase cascade
- JAK-RUSH pathway [6][7]
- PI3K/AKT/mTOR pathway [8]
This is my sandbox. This is where I edit my drafts.
- ^ Brooks, Charles L. (2012-08-01). "Molecular Mechanisms of Prolactin and Its Receptor". Endocrine Reviews. 33 (4): 504–525. doi:10.1210/er.2011-1040. ISSN 0163-769X. PMC 3410225. PMID 22577091.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Minh Hung, Huynh; Dieu Hang, Tran; Nguyen, Minh Tho (2019-06-13). "Structural Investigation of Human Prolactin Receptor Transmembrane Domain Homodimerization in a Membrane Environment through Multiscale Simulations". The Journal of Physical Chemistry. B. 123 (23): 4858–4866. doi:10.1021/acs.jpcb.9b01986. ISSN 1520-5207. PMID 31099581.
- ^ Dandawate, Prasad; Kaushik, Gaurav; Ghosh, Chandrayee; Standing, David; Ali Sayed, Afreen Asif; Choudhury, Sonali; Subramaniam, Dharmalingam; Manzardo, Ann; Banerjee, Tuhina; Santra, Santimukul; Ramamoorthy, Prabhu (April 2020). "Diphenylbutylpiperidine Antipsychotic Drugs Inhibit Prolactin Receptor Signaling to Reduce Growth of Pancreatic Ductal Adenocarcinoma in Mice". Gastroenterology. 158 (5): 1433–1449.e27. doi:10.1053/j.gastro.2019.11.279. ISSN 1528-0012. PMC 7103550. PMID 31786131.
- ^ Trott, J. F.; Schennink, A.; Petrie, W. K.; Manjarin, R.; VanKlompenberg, M. K.; Hovey, R. C. (May 2012). "Triennial Lactation Symposium: Prolactin: The multifaceted potentiator of mammary growth and function". Journal of Animal Science. 90 (5): 1674–1686. doi:10.2527/jas.2011-4682. ISSN 1525-3163. PMID 22205663.
- ^ Freeman, M. E.; Kanyicska, B.; Lerant, A.; Nagy, G. (October 2000). "Prolactin: structure, function, and regulation of secretion". Physiological Reviews. 80 (4): 1523–1631. doi:10.1152/physrev.2000.80.4.1523. ISSN 0031-9333. PMID 11015620.
- ^ Helmer, Rebecca A.; Panchoo, Marlyn; Dertien, Janet S.; Bhakta, Suhani M.; Hewetson, Aveline; Chilton, Beverly S. (2010-08-30). "Prolactin-induced Jak2 phosphorylation of RUSH: a key element in Jak/RUSH signaling". Molecular and cellular endocrinology. 325 (1–2): 143–149. doi:10.1016/j.mce.2010.05.010. ISSN 0303-7207. PMC 2902710. PMID 20562009.
- ^ Helmer, Rebecca A.; Dertien, Janet S.; Chilton, Beverly S. (2011-05-16). "Prolactin induces Jak2 phosphorylation of RUSHY195". Molecular and Cellular Endocrinology. 338 (1–2): 79–83. doi:10.1016/j.mce.2011.03.009. ISSN 1872-8057. PMID 21457752.
- ^ CLEVENGER, CHARLES V.; FURTH, PRISCILLA A.; HANKINSON, SUSAN E.; SCHULER, LINDA A. (February 2003). "The Role of Prolactin in Mammary Carcinoma". Endocrine reviews. 24 (1): 1–27. doi:10.1210/er.2001-0036. ISSN 0163-769X. PMC 1698952. PMID 12588805.