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Elucidating the Molecular Architecture of the 慣1D-AR:PDZ-Protein Macromolecular Complex

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서명/저자사항Elucidating the Molecular Architecture of the 慣1D-AR:PDZ-Protein Macromolecular Complex.
개인저자Harris, Dorathy-Ann Alyssa.
단체저자명University of Washington. Pharmacology.
발행사항[S.l.]: University of Washington., 2019.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2019.
형태사항131 p.
기본자료 저록Dissertations Abstracts International 81-02B.
Dissertation Abstract International
ISBN9781085694438
학위논문주기Thesis (Ph.D.)--University of Washington, 2019.
일반주기 Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
Advisor: Hague, Christopher.
이용제한사항This item must not be sold to any third party vendors.This item must not be added to any third party search indexes.
요약G Protein-Coupled Receptors (GPCRs) are seven transmembrane proteins that are the targets for over 30% of all medications currently on the market. Adrenergic Receptors (ARs) are one type of GPCR that responds to the endogenous catecholamines norepinephrine (NE) and epinephrine(Epi). In the AR family, there are three types: 慣1-, 慣2-, and 棺-ARs. Within each of these subfamilies are three subtypes and the Hague lab focuses one of these receptors: the 慣1D-AR. The 慣1D-AR is an interesting receptor in that it is very difficult to study due to its intracellular localization. There are no known cell lines that express endogenous 慣1D-ARs and within 48 hours after removing epithelial cell expressing the 慣1D-AR at the membrane, the receptor becomes localized to the endoplasmic reticulum (ER).Studying the 慣1D-AR is clinically important as there are many disorders that are influenced by this receptor. For example, it can impact urine flow in older males, due to benign prostate hypertrophy (BPH). The 慣1D-AR is also vital in the circulatory system in repairing blood vessels after injury as well as stimulus-induced movement. Also of note is the role the 慣1D-AR plays in both schizophrenia and post-traumatic stress disorder (PTSD, Raskind et. al. 2018). It has been noted that treatment with antagonists will decrease the reoccurrence of nightmares in veterans with PTSD. However, most antagonists have major toxic side effects that are associated with taking these medications. Thus, it is vital to determine how the 慣1D-AR signals with its PDZ and non PDZ proteins as a potential to create new therapeutics for PTSD, schizophrenia, BPH, and cardiovascular disease.Previously, the Hague laboratory determined that there may be a cell line that endogenously expresses the 慣1D-AR. Through mass spectrometry, it was determined that SW480 cells (a colorectal cancer cell line
일반주제명Molecular biology.
Cellular biology.
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