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Lam, Wai Kwan. "Investigation of interaction between solube adenylyl cyclase and p34SEI-1 /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202010%20LAM.
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García-Jiménez, Angela. "G-proteins and adenylyl cyclase in Alzheimer's disease postmortem brain /." Stockholm : [Karolinska institutets bibl.], 2002. http://diss.kib.ki.se/2002/91-7349-103-9.
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Halim, Kaha Desi, and 彭綺琼. "Protein phosphorylation in PC-12 cells induced by pituitary adenylate cyclase activating polypeptide 38." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31220861.
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Desi, Halim Kaha. "Protein phosphorylation in PC-12 cells induced by pituitary adenylate cyclase activating polypeptide 38 /." Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20793029.
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Wadman, Isobel A. "The regulation of human platelet adenylate cyclase by ATP and guanine nucleotide binding proteins." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241124.
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Coyle, Donna L. (Donna Lynn). "Modification of Cardiac Membrane Gsα by an Endogenous Arginine-Specific Mono-Adp-Ribosyltransferase." Thesis, University of North Texas, 1993. https://digital.library.unt.edu/ark:/67531/metadc332726/.
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The mechanism by which nicotinamide adenine dinucleotide (NAD) stimulates the activity of adenylate cyclase (AC) in canine plasma membrane has been studied. Using [3 2P]-NAD, the activation by NAD was correlated with the radiolabeling of the stimulatory guanosine triphosphate (GTP) binding protein Gsa. Further characterization demonstrated that the modification occurred only in the presence of G-protein activators and that arginine residue(s) were modified by ADP-ribose by the action of a mono-ADP-ribosyltransferase. Inhibitors of the transferase blocked both the modification of Gsa and the activation of AC. Collectively, these studies suggest that ADP-ribosylation of Gsa by an endogenous mono-ADP-ribosyltransferase may regulate cardiac AC.
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Baragli, Alessandra. "Assembly and function of multimeric adenylyl cyclase signalling complexes." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111888.
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G protein coupled receptors, G proteins and their downstream effectors adenylyl cyclase (ACs) were thought to transiently interact at the plasma membrane by random collisions following agonist stimulation. However a growing number of studies have suggested that a major revision of this paradigm was necessary to account for signal transduction specificity and efficiency. The revised model suggests that signalling proteins are pre-assembled as stable macromolecular complexes together with modulators of their activity prior to receptor activation. How and where these signalling complexes form and the mechanisms governing their assembly and maintenance are not completely understood yet. Initially, we addressed this question by exploring AC2 interaction with beta2-adrenergic receptors (beta2ARs) and heterotrimeric G proteins as parts of a pre-assembled signalling complex. Using a combination of biophysical and biochemical techniques, we showed that AC2 interacts with them before it is trafficked to the cell surface in transfected HEK-293 cells. These interactions are constitutive and do not require stimulation by receptor agonists. Furthermore, the use of dominant-negative Rab/Sar monomeric GTPases and dominant-negative heterotrimeric G protein subunits proved that AC2/beta2AR and AC2/Gbetagamma interactions occurred in the ER as measured using both BRET and co-immunoprecipitation experiments, while interaction of the Galpha subunits with the above complexes occurred at a slightly later stage. Both Galpha and Gbetagamma played a role in stabilizing these complexes. Our data also demonstrated that stimulation of AC was still possible when the complex remained on the inside of the cell but was reduced when the GalphaS/AC2 interaction was blocked, suggesting that the addition of the GalphaS subunit was required to render the nascent complexes functional prior to trafficking to proper sites of action. Next, we tackled the issue of higher order assembly of effectors and G proteins, using two different AC isoforms and GalphaS as a model. We demonstrated that AC2 can form heterodimers with AC5 through direct molecular interaction in unstimulated HEK-293 cells. AC2/5 heterodimerization resulted in a reduced total level of AC2 expression, which affected cellular accumulation of cAMP upon forskolin stimulation. The AC2/5 complex was stable in presence of receptor or forskolin stimulation. We provided evidence that co-expression with GalphaS increased the affinity of AC2 for AC5 as monitored by BRET. In particular, the complex formed by AC2/5 lead to synergistic accumulation of cAMP in presence of GalphaS and forskolin, with respect to either of the parent AC isoforms themselves. Finally, we also showed that this complex can be detected in native tissues, as AC2 and AC5 could be co-immunoprecipiated from lysates of mouse heart. Taken together, we provided evidence for stable formation of signalling complexes involving receptor/G proteins/adenylyl cyclase or G proteins/heterodimeric adenylyl cyclases and that G proteins play a crucial role for their assembly and function.
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Nielsen, Mark David. "Regulation of two subfamilies of adenylyl cyclase by Gi-coupled receptors : a possible role during cAMP-dependent synaptic plasticity in the Hippocampus /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/6247.
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Mahlapuu, Riina. "Signalling of galanin and amyloid precursor protein through adenylate cyclase /." Online version, 2004. http://dspace.utlib.ee/dspace/bitstream/10062/1245/5/Mahlapuu.pdf.
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Dimmock, Simon Andrew. "The role of adenylate cyclase-associated protein in higher plant development." Thesis, Durham University, 2005. http://etheses.dur.ac.uk/2010/.
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The Actin Cytoskeleton is essential for Eukaryotic life and is involved in a diverse range of cellular functions. Cyclase Associated Protein (CAP) was first identified in yeast as a regulator of the CYR1 Adenylate Cyclase. Subsequently CAP family members have been identified in every Eukaryotic kingdom and have also been implicated in the regulation of Actin dynamics. It has been proposed that the CAP family promotes the recycling of Actin monomers by cooperating with members of the Profilin and Actin Depolymerising Factor families. This study represents an attempt to investigate the function and developmental role of AtCAP1, an Arabidopsis member of the CAP family. Arabidopsis thaliana is widely used as a model for higher plant development due to its small sequenced genome and the availability of a wide variety of mutants. The elimination of AtCAP1 expression results in a distinct developmental phenotype. Early characteristics include the absence of the root hair collar, reduced root hair initiation and extension. Later onset phenotypes include reduced plant height and a severe reduction in pollen viability. In vivo studies of the CAP-deficient cytoskeleton reveal a distinct loss of fine filamentous Actin and the appearance of dense Actin aggregates. Cell expansion is also significantly reduced. The interaction between AtCAP1 and F-Actin is demonstrated in vitro by a biochemical interaction study and a filament bundling activity is suggested. The multimerisation of AtCAP1 and its interaction with other components of the Actin Cytoskeleton are demonstrated via Yeast Two Hybrid interactions. It is concluded that AtCAP1 is essential for the organisation of the plant cells F-Actin network and that this in turn is required for correct growth and development. It is hypothesised that AtCAP1 function is mediated by regulating the interaction between F-Actin and other Actin-interacting proteins.
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Baum, Kristen Michelle. "Characterization of two domains of Schizosaccharomyces pombe adenylate cyclase." Thesis, Boston College, 2005. http://hdl.handle.net/2345/405.
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Thesis advisor: Charles S. HoffmanGlucose detection in yeast occurs via a cAMP signaling pathway that is similar to that of other signaling pathways in humans. The presence of glucose in the environment ultimately represses, as a result of cAMP signaling, the transcription of the gene fbp1. Adenylate cyclase is known to convert ATP to cAMP, and is thus a central protein in the propagation of the signal. Mutant forms of the adenylate cyclase gene (git2) have been found by the inability for the organism to repress fbp1 transcription in the presence of glucose. In this study, two questions were under investigation. The first was focused on the ability of the mutations to affect the dimerization of the catalytic domain. The second investigated multiple protein-protein interactions in the leucine rich-repeat (LRR) domain of adenylate cyclase. Both domains contain mutations that confer an activation defect, and they are thus are thought to have a relationship
Thesis (BS) — Boston College, 2005
Submitted to: Boston College. College of Arts and Sciences
Discipline: Biology
Discipline: College Honors Program
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VanBennekom, Neyda. "Cholera toxin activates the unfolded protein response through an adenylate cyclase-independent mechanism." Master's thesis, University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5880.
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Cholera toxin (CT) is a bacterial protein toxin responsible for the gastrointestinal disease known as cholera. CT stimulates its own entry into intestinal cells after binding to cell surface receptors. Once internalized, CT is delivered via vesicle-mediated transport to the endoplasmic reticulum (ER), where the CTA1 subunit dissociates from the rest of the toxin and is exported (or translocated) into the cytosol. CTA1 translocates from the ER lumen into the host cytosol by exploiting a host quality control mechanism called ER-associated degradation (ERAD) that facilitates the translocation of misfolded proteins into the cytosol for degradation. Cytosolic CTA1, however, escapes this fate and is then free to activate its target, heterotrimeric G-protein subunit alpha (Gs?), leading to adenlyate cyclase (AC) hyperactivation and increased cAMP concentrations. This causes the secretion of chloride ions and water into the intestinal lumen. The result is severe diarrhea and dehydration which are the major symptoms of cholera. CTA1's ability to exploit vesicle-mediated transport and ERAD for cytosolic entry demonstrates a potential link between cholera intoxication and a separate quality control mechanism called the unfolded protein response (UPR), which up-regulates vesicle-mediated transport and ERAD during ER stress. Other toxins in the same family such as ricin and Shiga toxin were shown to regulate the UPR, resulting in enhanced intoxication. Here, we show UPR activation by CT, which coincides with a marked increase in cytosolic CTA1 after 4 hours of toxin exposure. Drug induced-UPR activation also increases CTA1 delivery to the cytosol and increases cAMP concentrations during intoxication. We investigated whether CT stimulated UPR activation through Gs? or AC. Chemical activation of Gs? induced the UPR and increased CTA1 delivery to the cytosol. However, AC activation did not increase cytosolic CTA1 nor did it activate the UPR. These data provide further insight into the molecular mechanisms that cause cholera intoxication and suggest a novel role for Gs? during intoxication, which is UPR activation via an AC-independent mechanism.M.S.
Masters
Molecular Biology and Microbiology
Medicine
Molecular and Microbiology
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Gupte, Raeesa Prashant. "Phosphoregulation of somatodendritic voltage-gated potassium channels by pituitary adenylate cyclase-activating polypeptide." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/5766.
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The endogenous neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) exerts various neuromodulatory functions in mammalian brain. Enhancement of synaptic activity, mediation of chronic inflammatory and neuropathic pain, and neuroprotection in cerebral ischemia reperfusion injury constitute some of the exemplary functions of PACAP. However, it remains unclear whether PACAP signaling can directly influence the function of critical voltage-gated ion channels, which could profoundly alter the excitability of neurons. Voltage-gated K+ (Kv) channels are critical regulators of neuronal excitability. The major Kv channel in the dendrites of mammalian neurons, Kv4.2, contributes most of the fast-activating and rapidly-inactivating K+ currents (IA), and is a key regulator of dendritic excitability, as well as modulation of synaptic inputs. In addition, the major somatic Kv channel Kv2.1 that contributes the bulk of slow-activating and non-inactivating K+ currents (IK), acts as an integrator of neuronal inputs and limits high frequency firing in neurons. As such, it provides homeostatic control of excitability under hyperexcitable and ischemic conditions. Both these Kv channels are known to undergo extensive post-translational modifications mainly by phosphorylation that alters their localization and biophysical properties. PACAP can activate its specific receptor PAC1 that could result in downstream activation of various kinases including protein kinase A (PKA), protein kinase C (PKC), extracellular signal-regulated kinase (ERK1/2). Therefore, I hypothesize that PACAP activation of PAC1 receptor can cause phosphorylation-dependent modulation of somatodendritic Kv4.2 and Kv2.1 channels, resulting in altered neuronal excitability.
First, I identified the various PAC1 receptor isoforms expressed in rat and mouse brain and elucidated that their activation by PACAP caused downstream PKA- and PKC-dependent signaling pathways, ultimately converging on ERK1/2 activation. Further, PACAP caused reduction in IA that was mediated by phosphorylation-dependent internalization of the channel protein from the plasma membrane. These effects were mediated by direct phosphorylation of the channel by ERK1/2 at the cytoplasmic C-terminus of the channel. Although PACAP did not significantly alter the voltage-dependence of Kv4.2 channel activation/inactivation, I observed distinct ERK1/2- and PKA-dependent changes in the extent and kinetics of channel inactivation.
Next, I observed that PACAP induced dephosphorylation of the Kv2.1 channel in CHN that was mediated by protein phosphatase 2A (PP2A), and was dependent on PKC activation but was independent of the effects of PACAP on Kv4.2 currents. Rapid but reversible dephosphorylation of Kv2.1 was also observed following induction of ischemia in neurons by oxygen-glucose deprivation (OGD). PACAP prolonged the dephosphorylation of Kv2.1 following in vitro ischemia-reperfusion and also reduced neuronal death. My results therefore suggest a novel PACAP/PAC1-PKC-PP2A-Kv2.1 signaling axis that provides neuroprotection during ischemia reperfusion injury.
In summary, my results suggest that PACAP can induce direct phosphorylation-dependent modulation of the Kv4.2 and Kv2.1 channel localization and function in mammalian brain neurons. The effect of PACAP on these two critical somatodendritic ion channels occurs via distinct signaling - convergent PKA-PKC-ERK-mediated phosphorylation of Kv4.2 channel, and PKC-PP2A-mediated dephosphorylation of the Kv2.1 channel. Such distinct modulations of these ion channels are presumably responsible for the multifarious roles of PACAP in the central nervous system.
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Sumner, Adriane Dee. "Pituitary Adenylate Cyclase Activating Polypeptide Signaling Alters Gene Expression In Chick Ciliary Ganglion Neurons." University of Toledo Health Science Campus / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=mco1217968374.
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Lee, Wai-him, and 李偉謙. "Proteomic analysis of protein phosphorylation in PC12 cells induced bypituitary adenylate cyclase activating polypeptide 38." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B30149885.
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Aasheim, Lise H. "Protein kinase C (PKC) amplifies the hormonal stimulation of adenylate cyclase in T51B rat liver cells." Thesis, University of Ottawa (Canada), 1990. http://hdl.handle.net/10393/5711.
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Membrane signalling is a process that is fundamental to the response of cells to extracellular stimuli. Two major pathways are used to generate intracellular "second messengers" in response to hormonal stimulation. They are the production of cAMP and hydrolysis of membrane phospholipids to produce inositol-1,4,5-trisphosphate and diacylglycerol. Recent evidence indicates that these two membrane signalling systems interact with one another. Activation of PKC by phorbol esters (TPA) results in a modification of the cAMP system leading to either attenuation or amplification of the cyclic AMP signal. It has been shown that TPA inhibits glucagon-stimulated adenylate cyclase activity in rat hepatocytes. In the non-neoplastic T51B rat liver cell line, TPA, when added to intact cells, had no effect on the basal level of cyclic AMP synthesis but caused a 1.5 fold amplification of the stimulation induced by $\beta$-adrenergic agents, cholera toxin and forskolin. The same concentration of TPA also caused translocation of PKC from the cytosolic fraction. The time course for the translocation is longer than the time course found for the enhancement of adenylate cyclase activity. The effect of TPA treatment seen in this tissue culture system appears to be activation of membrane associated PKC rather than translocation. Activation of PKC already present in the membrane is likely to cause a change in adenylate cyclase activity.
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Soparkar, Charles Nicholas Sidhartha. "Phenotypic and Biochemical Characterization of Cells Expressing a Gas/Gai Chimeric Protein: a Thesis." eScholarship@UMMS, 1988. http://escholarship.umassmed.edu/gsbs_diss/303.
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G-proteins are heterotrimeric complexes composed of α, β, and τ subunits and are involved in coupling receptor and effector functions during signal transduction across plasma membranes. G-proteins Gs and Gi are stimulatory and inhibitory to the catalytic subunit of adenylyl cyclase, respectively. A chimeric G-protein α subunit cDNA was constructed from the complete 5' untranslated region of Gαs52 (the 52 kD α subunit of Gs), the first 356 codons of the rat Gαs52, and the last 36 codons and 428 bp of the 3' untranslated region of the rat Gai2 (the α subunit of Gi2) cDNA. Expression of the chimeric G-protein alpha subunit (Gαs/i(38)) causes a constitutive increase in adenylyl cyclase activity in three different fibroblast cell lines. In turn, the elevated cyclase activity leads to higher levels of basal cyclic AMP and protein kinase A activity. The effect of Gαs/i(38) on cyclase does not seem to be through an inhibiton of Gαi function, but instead appears to be the consequence of direct action on the catalytic subunit, resulting in both a decreased time required for maximal cyclase activation and a greater maximal activation as well. Such alterations are not noted in cells expressing exogenous, wild-type Gαs. This data is based primarily on reconstitution assays using cholate extracts from fibroblast Gαs/i(38) clones and membranes derived from the S49 murine T-cell lymphoma (cyc- variant). Endogenous G-protein steady-state changes were detected by immunoblot analysis, but do not appear to account for the observed phenotypic alterations in Gαs/i(38) expressing clones. Furthermore, the validity of the above findings is unequivocally demonstrated through the use of amethopterin-mediated amplification of the chimeric Gαs/i(38) gene transcript and the consequent activation of adenylyl cyclase.
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BEUVE, ANNIE. "Adenylate cyclase de rhizobium meliloti : analyse du site actif et definition d'un motif commun aux proteines fixant les nucleotides." Paris 6, 1992. http://www.theses.fr/1992PA066412.
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L'adenylate cyclase (ac) est un enzyme responsable de la synthese d'ampc. Ce messager etant largement distribue, le postulat d'utiliser les acs comme temoins de l'evolution a ete pose. La caracterisation de l'ac de r. Meliloti a ainsi ete realisee. Une fusion avec le gene lacz d'e. Coli a permis la purification de l'hybride ac-bgalactosidase. Les caracteristiques biochimiques de cet enzyme ont ete determinees. Cette ac a des identites avec les acs et gcs eucaryotes. Cette identite de sequence avec des gcs et une forte inhibition de son activite par le gtp amena a l'etude du site actif par modification de sa specificite de substrat. Nous avons recherche par mutagenese au hasard de cette ac, des mutants exprimant une activite gc apres avoir construit un crible phenotypique detectant cette activite chez e. Coli. Cela a permis de determiner une partie du site actif des cyclases. Cette region ainsi definie comme nouveau site de fixation des nucleotides triphosphates (ntp) a ete retrouvee chez d'autres proteines fixant l'atp: les atpases a intermediaire phosphoryle. Un deuxieme consensus commun a ete mis en evidence. Ces deux enzymes qui catalysent des reactions differentes ont la meme poche de fixation des ntp. La structure transmembranaire des atpases est similaire a celle des acs eucaryotes et typique de toute une famille de transporteurs. Cela nous permet de proposer que ces enzymes derivent d'un transporteur fixant l'atp. Une dissection plus fine de ce site actif a ete entreprise par mutagenese dirigee. Elle met en evidence l'implication, dans le site actif, de 3 des 4 regions communes aux acs et gcs
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Smith, David M. "A role for adenylyl cyclase and the CREB/CRE transctiptional pathway in mammalian behavior /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/6296.
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Stanton, Suzanne Louise. "Homology Modeling and Molecular Docking of Antagonists to Class B G-Protein Coupled Receptor Pituitary Adenylate Cyclase Type 1 (PAC1R)." ScholarWorks @ UVM, 2016. http://scholarworks.uvm.edu/graddis/624.
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Recent studies have identified the Class B g-protein coupled receptor (GPCR) pituitary adenylate cyclase activating polypeptide type 1 (PAC1R) as a key component in physiological stress management. Over-activity of neurological stress response systems due to prolonged or extreme exposure to traumatic events has led researchers to investigate PAC1R inhibition as a possible treatment for anxiety disorders such as post-traumatic stress disorder (PTSD). In 2008, Beebe and coworkers identified two such small molecule hydrazide antagonists and a general pharmacaphore for PAC1R inhibition. However, a relative dearth of information about Class B GPCRs in general, and PAC1R in specific, has significantly hindered progress toward the development of small molecule antagonists of PAC1R. The recent crystallization of the homologically similar glucagon receptor (GCGR) by Siu and coworkers in 2013, also a Class B receptor, has provided an experimentally resolved template from which to base computationally derived models of PAC1R.
Initially, this research was focused towards synthesizing small molecule antagonists for PAC1R which were to be biologically screened via a qualitative western blot assay followed by a radioisotope binding assay for those hydrazides exhibiting down-stream signaling inhibitory capabilities. However, the resolution of the GCGR crystal structure shifted research objectives towards developing a homology model of PAC1R and evaluating that computationally created model with Beebe's known small molecule antagonists. Created using academic versions of on-line resources including UniProtKB, Swiss-Model and Maestro, a homology model for PAC1R is presented here. The model is validated and evaluated for the presence of conserved Class B GPCR residues and motifs, including expected disulfide bridges, a conserved tyrosine residue, a GWGxP motif, a conserved glutamic acid residue and the extension of the transmembrane helix 1 (TM1) into the extra-cellular domain.
Having determined this virtual PAC1R an acceptable model, ligand docking studies of known antagonists to the receptor were undertaken using AutoDock Vina in conjunction with AutoDock Tools and PyMol. Computational docking results were evaluated via comparison of theoretical binding affinity results to Beebe's experimental data. Based on hydrogen bonding capabilities, several residues possibly key to the ligand-receptor binding complex are identified and include ASN 240, TYR 241 and HIST 365. Although the docking software does not identify non-bonding interactions other than hydrogen-bonding, the roles of additional proposed binding pocket residues are discussed in terms of hydrophobic interactions, π-π interactions and halogen bonding. These residues include TYR 161, PHE 196, VAL 203, PHE 204, ILE 209, LEU 210, VAL 237, TRP 297, PHE 362 and LEU 386. Although theoretical in nature, this reported homology modeling and docking exercise details a proposed binding site that may potentially further the development of drugs designed for the treatment of PTSD.
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Shahidullah, Mohammad, Amritlal Mandal, and Nicholas A. Delamere. "A Role for Calcium-Activated Adenylate Cyclase and Protein Kinase A in the Lens Src Family Kinase and Na,K-ATPase Response to Hyposmotic Stress." ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017. http://hdl.handle.net/10150/625814.
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PURPOSE. Na, K-ATPase activity in lens epithelium is subject to control by Src family tyrosine kinases (SFKs). Previously we showed hyposmotic solution causes an SFK-dependent increase in Na, K-ATPase activity in the epithelium. Here we explored the role of cAMP in the signaling mechanism responsible for the SFK and Na, K-ATPase response. METHODS. Intact porcine lenses were exposed to hyposmotic Krebs solution (200 mOsm) then the epithelium was assayed for cAMP, SFK phosphorylation (activation) or Na, K-ATPase activity. RESULTS. An increase of cAMP was observed in the epithelium of lenses exposed to hyposmotic solution. In lenses exposed to hyposmotic solution SFK phosphorylation in the epithelium approximately doubled as did Na, K-ATPase activity and both responses were prevented by H89, a protein kinase A inhibitor. The magnitude of the SFK response to hyposmotic solution was reduced by a TRPV4 antagonist HC067047 added to prevent TRPV4-mediated calcium entry, and by a cytoplasmic Ca2+ chelator BAPTA-AM. The Na, K-ATPase activity response in the epithelium of lenses exposed to hyposmotic solution was abolished by BAPTA-AM. As a direct test of cAMP-dependent SFK activation, intact lenses were exposed to 8-pCPT-cAMP, a cell-permeable cAMP analog. 8-pCPT-cAMP caused robust SFK activation. Using Western blot, two calcium-activated adenylyl cyclases, ADCY3 and ADCY8, were detected in lens epithelium. CONCLUSIONS. Calcium-activated adenylyl cyclases are expressed in the lens epithelium and SFK activation is linked to a rise of cAMP that occurs upon hyposmotic challenge. The findings point to cAMP as a link between TRPV4 channel-mediated calcium entry, SFK activation, and a subsequent increase of Na, K-ATPase activity.
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Athos, Jaime Ian. "Calcium-stimulated signal transduction in long-term memory formation and neural plasticity /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/10641.
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Simos, Demetrios. "Studies on the mechanism of action of New Pressor Protein, bradykinin, pituitary adenylate cyclase-activating polypeptide and adrenal catecholamines as possible mediators of its cardiovascular effects." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ63202.pdf.
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Brami, Brigitte. "Modulation de l'activité adénylate cyclase du cortex surrénal bovin par l'angiotensine II et les activateurs potentiels de la protéine kinase C." Grenoble 1, 1988. http://www.theses.fr/1988GRE10015.
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Pineda, Victor Viray. "A genetic and pharmacological dissection of synaptic plasticity in the hippocampus /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/6290.
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Cannella, Sara Elisabetta. "Effect of CyaA acylation on its folding and membrane properties." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC198.
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L’Adénylate cyclase (CyaA), produite par B. pertussis, agent responsable de la coqueluche, est un des principaux facteurs de virulence de la bactérie. La toxine est une grande protéine multi-domaine qui est synthétisée comme un précurseur inactif, proCyaA. Ce précurseur est converti dans la forme active après une acylation spécifique. Après la sécrétion, la toxine envahir les cellules eucaryotes par un mécanisme unique qui implique la translocation de son domaine catalytique dans le cytosol des cellules eucaryotiques. Cette mécanisme est toujours pas clair et nombreuses questions restent ouvertes. Dans la présente étude, nous avons étudié les propriétés structurales et fonctionnelles des différentes espèces de (pro)CyaA en solution et inséré dans la membrane. Nous avons observé que le repliement de (pro)CyaA dans la forme monomérique dépend de la présence de calcium et de l'acylation post-traductionnelle. En outre, nous avons observé que la présence du calcium améliore fortement la stabilité de la protéine. De plus, nous avons identifié un segment hydrophobe dans CyaA, mais pas dans proCyaA, qui intervient dans les premières étapes du repliement de la protéine. L'analyse macroscopique a révélé que CyaA est plus stable et compacte par rapport à proCyaA. Nous avons aussi observé que les deux toxines sont capables de perméabiliser les membranes in vitro, mais que seulement la toxine monomérique et acyle est capable d'exercer des activités de membranes efficaces dans la cellule (hémolyse, translocation de AC et production de cAMP). Nous proposons que la toxine monomérique est la seul espèce compétent et fonctionnelAdenylate cyclase is one of the major virulence factors produced by Bordetella pertussis, the causative agent of whopping cough. The toxin is a huge multi-domain protein synthesized as an inactive precursor, proCyaA, which is converted into the active form upon a specific acylation. Once secreted across the bacterial cell envelope, the toxin invades eukaryotic cells through a unique mechanism that involves the direct translocation of its catalytic domain inside the cytosol of the target cells. This mechanism is still not clear and many questions remain open. In the present study we investigated the structural and functional properties of various (pro)CyaA species in solution and upon membrane-insertion. We found that the (re)folding of CyaA into a monomeric form critically depend upon the presence of calcium and the post-translational acylation. We observed that calcium binding strongly improves the stability of the protein. Moreover we identified a hydrophobic segment in CyaA, but not in proCyaA, which is involved in the early stages of the refolding process. Macroscopic analysis showed that CyaA is more stable and compact as compared to proCyaA. We also observed that both toxins are able to permeabilize membranes in vitro, although only the monomeric and acylated toxin is able to exert efficient membrane activities in cellula (i.e., hemolysis, AC translocation and cAMP production). We propose that the monomeric species is the functional competent and active state and that the acyl chains play not only a structural role but are also essential for the functional activities of the toxin
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Breuiller, Michelle. "Les recepteurs adrenergiques dans le myometre humain gravide : implication des recepteurs beta-adrenergiques chez la rate au moment de la parturition." Paris 7, 1988. http://www.theses.fr/1988PA077019.
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Beeler, Jeff A. "The role of the C1B region in the regulation of adenylyl cyclase : development and characterization of a soluble model C1B protein, 7C1B-S /." 2003. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3108050.
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Thesis (Ph. D.)--University of Chicago, Committee on Neurobiology, December 2003.CD-ROM includes PDF files of the entire dissertation and of the figures alone. Includes bibliographical references. Also available on the Internet.
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Hatley, Mark Edward. "Allosteric determinants of guanine nucleotide binding proteins and methods to crystallize the cytosolic domains of adenylyl cyclase." 2004. http://edissertations.library.swmed.edu/pdf/HatleyM050404/HatleyMark.pdf.
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Mbah, Andreas Nji. "Molecular regulation of universal stress proteins in environmentally mediated schistosomiasis parasites." Thesis, 2014. http://hdl.handle.net/10500/13382.
Full textAbstract:
Human schistosomiasis popularly known as bilharzias in many regions of Africa is a freshwater snail-transmitted disease caused by parasitic flatworms known as schistosomes. The growth and development of schistosomes typically requires developmental stages in multiple hosts and transmission stages in freshwater. These life cycle environments present a plethora of stressors. Certain gene families including heat shock proteins (HSPs/Hsps) and universal stress proteins (USPs) help schistosomes to respond to unfavourable conditions.
The availability of genomes sequences information for Schistosoma japonicum, Schistosoma mansoni and Schistosoma haematobium provide unique research resources to apply bioinformatics analysis of its associated USPs to predict regulatory features from sequence analysis. The objectives of the research were to (i) Infer the biochemical and environmental regulation of universal stress proteins of Schistosoma species; (ii) Identify biological function relevant protein sequence and structure features for prioritized universal stress proteins from Schistosoma species; (iii) Determine the distinctive structural features of a predicted regulator of Schistosoma adenylate cyclase activity that has possible influence on the functioning of universal stress proteins.
The findings revealed that (i) schistosomes USPs are hydrophilic and very reactive in the water environment or in aqueous phase, which seems
adaptive with their immediate environment and developmental stages; (ii) The functions of Smp_076400 and Sjp_0058490 (Q86DW2) are regulated by conserved binding site residues and metallic ions ligands (Ca2+, Mg2+ and Zn2+), particularly Ca2+ predicted to bind to both USPs; (iii) The S. mansoni life cycle and stress resistance pathway protein (Smp_059340.1) is regulated by Ser53, Thr188, Gly210 and Asp207 residues. The overall scope has highlighted the role of bioinformatics in predicting exploitable regulatory features of schistosome universal stress proteins and biological pathways that might lead to identification of putative functional biomarkers of common environmental diseases. The findings of this research can be applicable to other areas of environmental health and environmental genomics.Environmental Sciences
(D. Litt et Phil. (Environmental Sciences)
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Klímová, Nela. "Úloha RTX domény v aktivitě adenylátcyklázového toxinu z Bordetella pertussis." Master's thesis, 2015. http://www.nusl.cz/ntk/nusl-342647.
Full textAbstract:
The adenylate cyclase toxin (CyaA) of Bordetella pertussis is a 1706-residue protein comprising an amino-terminal adenylate cyclase (AC) domain and a carboxy-terminal Repeat-in-Toxin (RTX) domain. The RTX domain is a hallmark of the family of RTX proteins, which are secreted from the cytosol of Gram-negative bacteria to the cell environment through the Type I Secretion System (T1SS). The RTX domain of CyaA consists of five blocks of RTX nonapetide repeats with a consensus sequence X-(L/I/V)-X-G-G-X-G- X-D. The aim of this work was to determine the role of the RTX domain in biological activities of CyaA and its role in the secretion of the toxin molecule from Bordetella pertussis. Systematic deletion analysis revealed that none of the prepared CyaA constructs was able to translocate its AC domain across the cytoplasmic membrane of host cells and make pores in target membranes. Moreover, deletion of individual RTX repeat blocks resulted in a very low efficacy of secretion of CyaA mutants into cell exterior. These data suggested that structural integrity of the RTX domain of CyaA is essential not only for cytotoxic activities of the toxin molecule but also for its secretion through the T1SS.
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Awungnjia, Asong John. "Recombinant Expression of a Putative F-box Protein from Arabidopsis tha/iana and Testing for its Possible Adenylate Cyclase Activity / Awungnjia, Asong John." Thesis, 2013. http://hdl.handle.net/10394/14699.
Full textAbstract:
Cyclic 3',5' adenosine monophosphate (cAMP) is a product of ATP hydrolysis catalyzed by
the enzymes adenylate cyclases (ACs). These two groups of molecules (cAMP and ACs)
have both been experimentally confirmed as key components and second messengers in the
cell signaling cascades of both animals and lower eukaryotes. They play a vital role in linking
environmental stimuli to physiological response in living cells. Although this information is
widely documented in animals and lower eukaryotes, in plants both the presence and
biological role of ACs are still very obscure and elusive. In this study, our work focused on
an Arabidopsis thaliana F-box protein (coded for by the At4g39756 gene), which recently
has been bioinfonnatically annotated as an AC candidate and at the same time, previously
been implicated in stress responses, for assessment of its possible adenylate cyclase activity.
In order to assess for this possible AC activity, we extracted total mRNA from 8-weeks old
Arabidopsis thaliana leaf material and used this mRNA as a template for the amplification of
the At4g39756 gene fragment bearing the putative AC catalytic center in the F-box domain
using RT-PCR technique. The amplified fragment was then cloned into a pCRT7/NT-TOPO
vector and the resultant recombinant construct (pCRT7/NT-TOPO:F-box) then subsequently
transformed into the expression host, Escherichia coli BL21 (DE3) Star pLysS cells. Positive
transformants were then cultured in a double strength Yeast-Trytone Soy broth and induced
with I Mm IPTG at an OD6oo 0.5 to express the recombinant F-box protein. The expressed
recombinant protein was found to be in its insoluble and non-native form and was therefore,
first purified on a Ni-NTA column under denaturing conditions followed by its re-naturing
into its native and soluble form via a linear gradient on the same colwnn. The resultant
protein product was then tested for its possible endogenous, in vitro and in vivo AC activities.
The endogenous and in-vitro AC activities were tested and determined by a cAMP-specific
enzyme immunoassaying system while the in-vivo activity was tested and determined via a
complementation testing. Results from all the three tests showed that this putative F-box
protein has some inherent endogenous, in-vitro and in-vivo adenylate cyclase activities and
therefore confirming it as a higher plant adenylate cyclase with a possible cAMP-mediated
signaling system.Thesis (M.Sc. (Biology) North-West University, Mafikeng Campus, 2013
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Kočková, Radka. "Vliv positivně inotropních a antiarytmických farmak na kardiovaskulární systém." Doctoral thesis, 2015. http://www.nusl.cz/ntk/nusl-333581.
Full textAbstract:
Heart rate changes mediate the embryotoxic effect of antiarrhythmic drugs in the chick embryo A significant increase in cardiovascular medication use during pregnancy has occurred in recent years but only limited evidence on its safety profile is available. We hypothesized that drug-induced bradycardia is the leading mechanism of developmental toxicity. We tested metoprolol, carvedilol, or ivabradine for embryotoxicity and their acute effect on chick embryonic model. We used video microscopy and ultrasound biomicroscopy. Significant dose-dependent mortality was achieved in embryos injected with carvedilol and ivabradine. In ED4 embryos, metoprolol, carvedilol and ivabradine reduced the heart rate by 33%, 27%, and 55%, respectively, compared to controls (6%). In ED8 embryos this effect was more pronounced with a heart rate reduction by 71%, 54%, 53%, respectively (controls 36%). Cardiac output decreased in all tested groups but only proved significant in the metoprolol group in ED8 embryos. The number of -adrenergic receptors showed a downward tendency during embryonic development but a negative chronotropic effect of tested drugs was increasingly pronounced with embryonic maturity. This effect was associated with reduced cardiac output in chick embryos, probably leading to premature death....
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Roberts, Wayne, S. Magwenzi, Ahmed Aburima, and Khalid M. Naseem. "Thrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP/protein kinase A signaling cascade." 2010. http://hdl.handle.net/10454/6155.
Full textAbstract:
Cyclic adenosine monophosphate (cAMP)-dependent signaling modulates platelet function at sites of vascular injury. Here we show that thrombospondin-1 (TSP-1) prevents cAMP/protein kinase A (PKA) signaling through a CD36-dependent mechanism. Prostaglandin E(1) (PGE(1)) induced a robust inhibition of both platelet aggregation and platelet arrest under physiologic conditions of flow. Exogenous TSP-1 reduced significantly PGE(1)-mediated inhibition of both platelet aggregation and platelet arrest. TSP-1 prevented PGE(1)-stimulated cAMP accrual and phosphorylation of PKA substrates, through a mechanism requiring phosphodiesterase3A. TSP-1 also inhibited VASP phosphorylation stimulated by the nonhydrolyzable cAMP analog, 8-bromo-cAMP, indicating that it may regulate cAMP-mediated activation of PKA. The inhibitory effect of TSP-1 on cAMP signaling could be reproduced with a peptide possessing a CD36 binding sequence of TSP-1, while the effects of TSP-1 were prevented by a CD36 blocking antibody. TSP-1 and the CD36 binding peptide induced phosphorylation of Src kinases, p38 and JNK. Moreover, inhibition of Src kinases blocked TSP-1-mediated regulation of cAMP concentrations and the phosphorylation of VASP, indicating that TSP-1 modulated the cAMP/PKA signaling events through a tyrosine kinase-dependent pathway downstream of CD36. These data reveal a new role for TSP-1 in promoting platelet aggregation through modulation of the cAMP-PKA signaling pathway.