A5038627142- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Protein Kinase Regulation and GTPase Signaling
- Neuroscience and Neuropharmacology Research
- Phosphodiesterase function and regulation
- Cardiac electrophysiology and arrhythmias
- Neuropeptides and Animal Physiology
- Pain Mechanisms and Treatments
- Peptidase Inhibition and Analysis
- Cellular transport and secretion
- Signaling Pathways in Disease
- Nitric Oxide and Endothelin Effects
- Cardiomyopathy and Myosin Studies
- Biochemical and Structural Characterization
- Adenosine and Purinergic Signaling
- Pregnancy-related medical research
- Chemical synthesis and alkaloids
- Heat shock proteins research
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- PI3K/AKT/mTOR signaling in cancer
- Glycosylation and Glycoproteins Research
- Sleep and Wakefulness Research
- Genetics, Bioinformatics, and Biomedical Research
- Protein Structure and Dynamics
The University of Texas Health Science Center at Houston
2015-2024
The University of Texas Health Science Center at San Antonio
2020-2021
Purdue University West Lafayette
2013-2019
Reproductive Science Center
2017
University of California, San Francisco
2017
Medizinische Hochschule Hannover
2017
University of Regensburg
2017
Chapman University
2017
Laboratoire d’immunologie intégrative du cancer
2016
University of Houston - Downtown
2015
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links open access knowledgebase source and their ligands (www.guidetopharmacology.org), which more detailed views target ligand properties. Although constitutes over 500 pages, material presented substantially reduced compared...
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties approximately 1800 drug targets, and about 6000 interactions with 3900 ligands. There an emphasis on selective pharmacology (where available), plus links open access knowledgebase source targets their ligands (www.guidetopharmacology.org), which more detailed views target ligand properties. Although constitutes almost 500 pages,...
Abstract G protein-coupled receptors (GPCRs), proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether ligand-dependent interactions between these molecules are based on random collisions or rearrangement pre-coupled elements in a macromolecular complex. Furthermore, remains controversial GPCR homodimer coupled to single heterotrimeric protein constitutes common functional unit. Using peptide-based approach, we...
The central adenosine system and receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by strategic co-localization different dopamine receptor subtypes two populations striatal efferent neurons, striatonigral striatopallidal, that give rise to direct indirect pathways, respectively. With optogenetic techniques it has been possible dissect differential pathways mediating "Go" responses upon exposure reward-related stimuli "NoGo"...
Forskolin- and Gsα-stimulated adenylyl cyclase activity is observed after mixture of two independently-synthesized ∼25-kDa cytosolic fragments derived from mammalian cyclases (native Mr ∼ 120,000). The C1a domain type V (VC1) the C2 II (IIC2) can both be expressed in large quantities purified to homogeneity. When mixed, their maximally stimulated specific activity, 150 μmol/min/mg protein, substantially exceeds values previously with intact enzyme. A soluble, high-affinity complex containing...
The stimulatory G protein α subunit G<sub>sα</sub> binds within a cleft in adenylyl cyclase formed by the α1-α2 and α3-β4 loops of C<sub>2</sub> domain. pseudosymmetry C<sub>1</sub> domains suggests that homologous inhibitory G<sub>iα</sub> could bind to analogous C<sub>1</sub>. We demonstrate myristoylated guanosine 5′-3-<i>O</i>-(thio)triphosphate-G<sub>iα1</sub> forms stable complex with (but not C<sub>2</sub>) domain type V cyclase. Mutagenesis membrane-bound enzyme identified residues...
The production of cAMP is controlled on many levels, notably at the level synthesis by enzyme adenylyl cyclase. We have recently identified a new regulator cyclase activity, RGS2, which decreases accumulation when overexpressed in HEK293 cells and inhibits vitro activity types III, V, VI In addition, RGS2 blocking antibodies lead to elevated levels olfactory neurons. Here we examine nature interaction between type V expressing cyclase, inhibited Galpha(s)-Q227L- or beta(2)-adrenergic...
The mechanism of P-site inhibition adenylyl cyclase has been probed by equilibrium binding measurements using 2′-[3H]deoxyadenosine, a inhibitor, and kinetic analysis both the forward reverse reactions (i.e. cyclic AMP ATP synthesis, respectively). There is one site for 2′-deoxyadenosine per C1/C2 heterodimer; K d 40 ± 3 μm. Binding observed only in presence products reaction, pyrophosphate (PPi). A substrate analog, Ap(CH2)pp (α,β-methylene adenosine 5′-triphosphate), compete PPi, but...
Adenylyl cyclase activity can be reconstituted by simple mixture of the two cytosolic domains enzyme after their independent synthesis in Escherichia coli. We have synthesized and purified C1a domain type I adenylyl C2 II to assess interactions with each other activators Gsalpha forskolin. In absence an activator, fragments associate low affinity display catalytic activity. This basal stimulated more than 100-fold either forskolin or activated Gsalpha. Further, addition these increases...
Spatiotemporal specificity of cAMP action is best explained by targeting protein kinase A (PKA) to its substrates A-kinase-anchoring proteins (AKAPs). At synapses in the brain, AKAP79/150 incorporates PKA and other regulatory enzymes into signal transduction networks that include β-adrenergic receptors, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA), N-methyl-d-aspartic acid receptors. We previously showed clusters with type 5 adenylyl cyclase (AC5) assemble a negative feedback...
Protein kinase A-anchoring proteins (AKAPs) play important roles in the compartmentation of cAMP signaling, anchoring protein A (PKA) to specific cellular organelles and serving as scaffolds that assemble localized signaling cascades. Although AKAPs have been recently shown bind adenylyl cyclase (AC), functional significance this association has not studied. In cardiac myocytes, muscle beta (mAKAPbeta) coordinates cAMP-dependent, calcium, MAP pathways is for hypertrophy. We now show...
A-kinase anchoring proteins (AKAPs) influence the spatial and temporal regulation of cAMP signaling events. Anchoring PKA in proximity to certain adenylyl cyclase (AC) isoforms is thought enhance phosphorylation dependent termination synthesis. Using a combination immunoprecipitation enzymological approaches, we show that plasma membrane targeted protein AKAP9/Yotiao displays unique specificity for interaction variety AC isoforms. Yotiao inhibits 2 3, but has no effect on 1 or 9, serving...
Nine membrane-bound adenylyl cyclase (AC) isoforms catalyze the production of second messenger cyclic AMP (cAMP) in response to various stimuli. Reduction AC activity has well documented benefits, including benefits for heart disease and pain. These roles have inspired development isoform-selective inhibitors, a lack which currently limits exploration functions and/or treatment dysfunctions involving AC/cAMP signaling. However, inhibitors described as AC5- or AC1-selective not been screened...
Abstract Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors, but rodent models of pain-related OA have concentrated on allodynia rather than pain, and generated non-nociceptive Aβ fibers nociceptors. Little is known about how or nociceptor generated. To define neurophysiological alterations underlying OA, we used isolated dorsal root ganglion neurons that continue generate after removal from animals displaying pain. We subclassify as either spontaneous solely...
Little is known about intracellular signaling mechanisms that persistently excite neurons in pain pathways. Persistent spontaneous activity (SA) generated the cell bodies of primary nociceptors within dorsal root ganglia (DRG) has been found to make major contributions chronic a rat model spinal cord injury (SCI) (Bedi et al., 2010; Yang 2014). The occurrence SCI-induced SA large fraction DRG and persistence this long after dissociation provide an opportunity define intrinsic chronically...