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Title: Molecular cloning and characterisation of G-protein-coupled receptors from the pituitary gland
Author: Duthie, Sarah MacDonald
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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This thesis describes molecular cloning and characterisation studies of two G-protein coupled receptors (GPRs), the thyrotrophin-releasing hormone receptor (TRH-R) and the dopamine D2 receptor. Sequence analysis identified the clone as a TRH-R encoding a putative protein of 398 amino acids. The human pituitary TRH-R had high sequence homology with the rat and mouse TRH-Rs, except at the 3' end of the carboxy (COOH) tail. In this region, residue 392 is a common point of sequence divergence, after which the human, rat and mouse TRH-Rs encode variant amino acids. The COOH tail of GPRs has been implicated in functionally significant events including receptor phosphorylation, desensitisation and possibly second messenger coupling. The human TRH-R clone was transiently expressed in COS-1 cells and showed high affinity receptor binding using [3H](3-Met-His2)TRH. Ultimately, the mouse TRH-R and D2-R genomic clones may be used to study the significance of possible splicing events in the regulation of prolactin secretion using transgenic mouse models. Information relating to the sequence and structural organisation of the genes encoding these GPRs will facilitate the identification of mutant receptors which may be involved in disease states. Analysis of receptor structure/function relationships will facilitate the study of ligand/receptor interactions, leading to the design of agonists and antagonists selective for a particular receptor subtype.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available