Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 16 of 16 for “"constitutive activity"”.
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Constitutive activity in orphan G protein coupled receptors
… to evaluate the extent of agonist independent constitutive signaling among orphan class-A G protein coupled receptors (GPCRs). These receptors translate extracellular signals via conformational change into intracellular activation of different G proteins and subsequent second messenger …
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Biased Constitutive Activity in the Uveal Melanoma Oncogene CYSLTR2 is Unique in CYSLTR2 Germline and Pan-Cancer Human Variome
… has been hypothesized to result from constitutive activity, but how the receptor could escape desensitization is unknown. In this work, we characterized the functional properties of CysLTR2-L129Q. CysLTR2 signals through the Gq/11/PLC-β pathways, so using a homogenous time resolved …
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Fusion Proteins as Selective Inducers of Constitutive Activity and Tools to Discriminate the Biased Signaling Profile of β2 Adrenoceptor Ligands
… β2AR-βarr2 in HEK293 cells by measuring their constitutive activity, transducer recruitment, and pharmacologic modulation. Our fusion proteins show (a) steric hindrance from the reciprocal endogenous transducers, (b) constitutive activity of the β2AR for the signaling pathway activated by the …
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The structure and function of the human ghrelin receptor
… The ghrelin-R displays a high degree of constitutive activity, signalling through the inositol phosphate pathway in the absence of bound agonist. TMs III and VI have been reported to be central to the activation of Family A GPCRs, with interactions between the two helices stabilising the …
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Molecular Signaling and Agonist Discovery for GPR52
… Gs and Golf to increase cAMP signaling, with constitutive activity driven by Gs. GPR52 is co-expressed with D2 dopamine receptors, and in vitro studies show crosstalk at the level of adenylyl cyclase and cAMP signaling. The constitutive activity of GPR52 allows for more dynamic modulation of …
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The role of the CCR5 co-receptor conformation in HIV fusion
… by site-directed mutagenesis and screened for constitutive activity using intracellutal signaling assays.
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An Investigation into the pharmacology of the ghrelin receptor
… displays a high level of ligand-independent (constitutive) activity and has been suggested to couple to Gaq/11, Gai/o, Gas and Ga12/13 G protein pathways, although little is known about the signalling of ghrelin and the growth hormone secretagogues in all but the Gaq/11 pathway. Two of the …
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Exploring the molecular signatures of the ligand-receptor-Gi/o protein interactions of adenosine A1 and A3 receptors
… of agonists. Also, hA1R showed much higher constitutive activity than hA3R in activating all six inhibitory G proteins. To investigate the structural mechanisms underlying this differential preference in activating the Gi/o proteins between hA1R and hA3R, the roles of 32 non-conserved …
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Probing Interactions Between Canonical NOX Domains
… in prokaryotes, namely bacteria. Due to their constitutive activity and solubility in detergent, bacterial NOXes, such as <em>Streptococcus Pneumoniae </em>NOX, have emerged as a model for studying NOXes. Past research studies in NOXes have identified conserved, putative interacting regions at …
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Discovery of Unique Antiviral Pathways in a Bat Viral Reservoir, the Black Flying Fox
… regulatory region of the protein that confer constitutive activity to bat IRF7. This work has uncovered two different mechanisms by which antiviral responses between bat and human hosts differ, and provides insight regarding how bats manage to keep numerous viral infections under control.
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Induced Degradation of G-Protein-Coupled Receptors Through Proteolysis Targeting Chimeras
… target oncogenic GPCRs that are overexpressed or constitutively active, as in the case of constitutively active mutants (CAMs), which have roles in cancer progression. TPD methods include proteolysis targeting chimeras (PROTACs), which are heterobifunctional molecules where one end has a ligand …
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Investigations into the use of maize streak virus as a gene vector
… coat protein promoter has low, but measurable constitutive activity in the absence of genome amplification, but that viral replication enhances coat protein expression about 45-fold. I found no evidence for Rep-mediated transactivation of the coat protein promoter.
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Regulation of the kRAS Promoter in Pancreatic Cancer by Proteins and Small Molecules
… kRAS is a proto-oncogene with intrinsic GTPase activity, that contributes to cell proliferation, division, and apoptosis. kRAS mutations are observed in >95% of pancreatic adenocarcinoma and in 30 % of all human tumors. Pancreatic cancer is the fourth most deadly cancer, with 5 year survival …
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Studies of Smoothened in Hedgehog Signaling Pathway
… not clear whether phosphorylation regulates Smo activity or not. In this study, I found that protein kinase A (PKA) and casein kinase I (CKI) regulate Smo cell surface accumulation and activity in response to Hh. PKA and CKI phosphorylate Smo directly at multiple sites which form three clusters …
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Characterization of Rimonabant effects on G protein activity
… many GPCRs have found to exhibit spontaneous activity, which can be blocked by ligands that are referred to as inverse agonists (Milligan, 2003). Cannabinoid CB1 receptor is one of the most abundant GPCR in the central nervous system, and is coupled to Gi/o proteins to inhibit adenylyl …
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Substrate Identification of an Oncogenic Kinase: Elucidating the Pathogenesis of a Rare Liver Cancer
… this cancer. While we have shown that the kinase activity of the fusion protein is essential for transformation, it is not currently known whether the oncogenic kinase that results from this fusion event, DNAJB1- PRKACA, phosphorylates the same substrates as PRKACA, the protein product of PRKACA. …