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https://www.readbyqxmd.com/read/28192412/akap-mediated-feedback-control-of-camp-gradients-in-developing-hippocampal-neurons
#1
Kirill Gorshkov, Sohum Mehta, Santosh Ramamurthy, Gabriele V Ronnett, Feng-Quan Zhou, Jin Zhang
Cyclic AMP (cAMP) and protein kinase A (PKA), classical examples of spatially compartmentalized signaling molecules, are critical axon determinants that regulate neuronal polarity and axon formation, yet little is known about micro-compartmentalization of cAMP and PKA signaling and its role in developing neurons. Here, we revealed that cAMP forms a gradient in developing hippocampal neurons, with higher cAMP levels in more distal regions of the axon compared to other regions of the cell. Interestingly, this cAMP gradient changed according to the developmental stage and depended on proper anchoring of PKA by A-kinase anchoring proteins (AKAPs)...
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28164467/microtubule-regulating-proteins-and-camp-dependent-signaling-in-neuroblastoma-differentiation
#2
Pablo Muñoz-Llancao, Cristian de Gregorio, Macarena Las Heras, Christopher Meinohl, Kevin Noorman, Erik Boddeke, Xiaodong Cheng, Frank Lezoualc'h, Martina Schmidt, Christian Gonzalez-Billault
Neurons are highly differentiated cells responsible for the conduction and transmission of information in the nervous system. The proper function of a neuron relies on the compartmentalization of their intracellular domains. Differentiated neuroblastoma cells have been extensively used to study and understand the physiology and cell biology of neuronal cells. Here, we show that differentiation of N1E-115 neuroblastoma cells is more pronounced upon exposure of a chemical analog of cyclic AMP (cAMP), db-cAMP...
March 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28119464/ser1928-phosphorylation-by-pka-stimulates-the-l-type-ca2-channel-cav1-2-and-vasoconstriction-during-acute-hyperglycemia-and-diabetes
#3
Matthew A Nystoriak, Madeline Nieves-Cintrón, Tommaso Patriarchi, Olivia R Buonarati, Maria Paz Prada, Stefano Morotti, Eleonora Grandi, Julia Dos Santos Fernandes, Katherine Forbush, Franz Hofmann, Kent C Sasse, John D Scott, Sean M Ward, Johannes W Hell, Manuel F Navedo
Hypercontractility of arterial myocytes and enhanced vascular tone during diabetes are, in part, attributed to the effects of increased glucose (hyperglycemia) on L-type CaV1.2 channels. In murine arterial myocytes, kinase-dependent mechanisms mediate the increase in CaV1.2 activity in response to increased extracellular glucose. We identified a subpopulation of the CaV1.2 channel pore-forming subunit (α1C) within nanometer proximity of protein kinase A (PKA) at the sarcolemma of murine and human arterial myocytes...
January 24, 2017: Science Signaling
https://www.readbyqxmd.com/read/28077322/a-protein-kinase-a-ezrin-complex-regulates-connexin-43-gap-junction-communication-in-liver-epithelial-cells
#4
Aleksandra R Dukic, Linda Hofstad Haugen, Guillaume Pidoux, Edward Leithe, Oddmund Bakke, Kjetil Taskén
Communication between adjacent cells can occur via gap junctions (GJ) composed of connexin (Cx) hexamers that allow passage of small molecules. One of the most widely and highly expressed Cxs in human tissues is Cx43, shown to be regulated through phosphorylation by several kinases including PKA. Ezrin is a membrane associated protein that can serve as an A-kinase anchoring protein (AKAP) and hold an anchored pool of PKA. Here, we used the liver epithelial cell line IAR20, which expresses Cx43 as the predominant GJ protein, to test the hypothesis that Ezrin may associate with Cx43 in cell types that form stable GJs and serve as an AKAP...
January 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28076805/regulation-of-active-icam-4-on-normal-and-sickle-cell-disease-rbcs-via-akaps-is-revealed-by-afm
#5
Jing Zhang, Krithika Abiraman, Sasia-Marie Jones, George Lykotrafitis, Biree Andemariam
Human healthy (wild-type (WT)) and homozygous sickle (SS) red blood cells (RBCs) express a large number of surface receptors that mediate cell adhesion between RBCs, and between RBCs and white blood cells, platelets, and the endothelium. In sickle cell disease (SCD), abnormal adhesion of RBCs to endothelial cells is mediated by the intercellular adhesion molecule-4 (ICAM-4), which appears on the RBC membrane and binds to the endothelial αvβ3 integrin. This is a key factor in the initiation of vaso-occlusive episodes, the hallmark of SCD...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28063348/the-in-silico-identification-of-small-molecules-for-protein-protein-interaction-inhibition-in-akap-lbc-rhoa-signaling-complex
#6
Asifullah Khan, Mehwish Munir, Sara Aiman, Abdul Wadood, Arif-Ullah Khan
The rational design of small molecules that mimic key residues at the interface of interacting proteins can be a successful approach to target certain biological signaling cascades causing pathophysiological outcome. The A-Kinase Anchoring Protein, i.e. AKAP-Lbc, catalyses nucleotide exchange on RhoA and is involved in cardiac repolarization. The oncogenic AKAP-Lbc induces the RhoA GTPase hyperactivity and aberrantly amplifies the signaling pathway leading to hypertrophic cardiomyocytes. We took advantage of the AKAP-Lbc-RhoA complex crystal structure to design in silico small molecules predicted to inhibit the associated pathological signaling cascade...
December 31, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28003270/akap-mediated-signalling-the-importance-of-being-in-the-right-place-at-the-right-time
#7
EDITORIAL
Cinzia Perrino, Bruno Trimarco
No abstract text is available yet for this article.
February 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/27901058/a-kinase-anchoring-protein-4-akap4-is-an-erk1-2-substrate-and-a-switch-molecule-between-camp-pka-and-pkc-erk1-2-in-human-spermatozoa
#8
Liat Rahamim Ben-Navi, Tal Almog, Zhong Yao, Rony Seger, Zvi Naor
Mammalian spermatozoa undergo capacitation and acrosome reaction in order to fertilize the egg. The PKC-ERK1/2 pathway plays an important role in human spermatozoa motility, capacitation and the acrosome reaction. Here we demonstrate that ERK1/2 phosphorylates proAKAP4 on Thr265 in human spermatozoa in vitro and in vivo. Cyclic AMP (cAMP) had no effect on ERK1/2 activity in human spermatozoa, but stimulated the MAPK in mouse pituitary LβT2 gonadotrope cells. cAMP via PKA attenuates PKC-dependent ERK1/2 activation only in the presence of proAKAP4...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27835919/pka-and-apicomplexan-parasite-diseases
#9
M Haidar, G Ramdani, E J Kennedy, G Langsley
The cAMP-dependent protein kinase PKA is a well-characterized member of the serine-threonine protein AGC kinase family and is the effector kinase of cAMP signaling. As such, PKA is involved in the control of a wide variety of cellular processes including metabolism, cell growth, gene expression and apoptosis. cAMP-dependent PKA signaling pathways play important roles during infection and virulence of various pathogens. Since fluxes in cAMP are involved in multiple intracellular functions, a variety of different pathological infectious processes can be affected by PKA signaling pathways...
November 11, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27813475/-role-and-regulation-of-camp-signaling-in-human-trophoblast-fusion
#10
REVIEW
Pascale Gerbaud, Fatima Ferreira, Guillaume Pidoux
In the human placenta, mononuclear cytotrophoblasts fuse to form multinucleated syncytia ensuring hormonal production and nutrient exchanges between the maternal and fetal circulation. The syncytial formation is necessary for the maintenance of pregnancy and for fetal growth. The cAMP signaling pathway is the major route to trigger trophoblast fusion and its activation results in phosphorylation of specific intracellular target proteins and assembly of macromolecular protein complexes constituting the fusogenic machinery at the plasma membrane...
2016: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/27693258/clustering-and-functional-coupling-of-diverse-ion-channels-and-signaling-proteins-revealed-by-super-resolution-storm-microscopy-in-neurons
#11
Jie Zhang, Chase M Carver, Frank S Choveau, Mark S Shapiro
The fidelity of neuronal signaling requires organization of signaling molecules into macromolecular complexes, whose components are in intimate proximity. The intrinsic diffraction limit of light makes visualization of individual signaling complexes using visible light extremely difficult. However, using super-resolution stochastic optical reconstruction microscopy (STORM), we observed intimate association of individual molecules within signaling complexes containing ion channels (M-type K(+), L-type Ca(2+), or TRPV1 channels) and G protein-coupled receptors coupled by the scaffolding protein A-kinase-anchoring protein (AKAP)79/150...
September 27, 2016: Neuron
https://www.readbyqxmd.com/read/27628689/a-cell-based-high-throughput-assay-for-gap-junction-communication-suitable-for-assessing-connexin-43-ezrin-interaction-disruptors-using-incucyte-zoom
#12
Aleksandra R Dukic, David W McClymont, Kjetil Taskén
Connexin 43 (Cx43), the predominant gap junction (GJ) protein, directly interacts with the A-kinase-anchoring protein (AKAP) Ezrin in human cytotrophoblasts and a rat liver epithelial cells (IAR20). The Cx43-Ezrin-protein kinase (PKA) complex facilitates Cx43 phosphorylation by PKA, which triggers GJ opening in cytotrophoblasts and IAR20 cells and may be a general mechanism regulating GJ intercellular communication (GJIC). Considering the importance of Cx43 GJs in health and disease, they are considered potential pharmaceutical targets...
September 14, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27487922/malonate-in-the-nucleotide-binding-site-traps-human-akap18%C3%AE-%C3%AE-in-a-novel-conformational-state
#13
Kaare Bjerregaard-Andersen, Ellen Østensen, John D Scott, Kjetil Taskén, Jens Preben Morth
A-kinase anchoring proteins (AKAPs) are a family of proteins that provide spatiotemporal resolution of protein kinase A (PKA) phosphorylation. In the myocardium, PKA and AKAP18γ/δ are found in complex with sarcoendoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and phospholamban (PLB). This macromolecular complex provides a means by which anchored PKA can dynamically regulate cytoplasmic Ca(2+) release and re-uptake. For this reason, AKAP18γ/δ presents an interesting drug target with therapeutic potential in cardiovascular disease...
August 2016: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/27484798/the-a-kinase-anchoring-protein-akap-glycogen-synthase-kinase-3%C3%AE-interaction-protein-gskip-regulates-%C3%AE-catenin-through-its-interactions-with-both-protein-kinase-a-pka-and-gsk3%C3%AE
#14
Alessandro Dema, Micha Friedemann Schröter, Ekaterina Perets, Philipp Skroblin, Marie Christine Moutty, Veronika Anita Deàk, Walter Birchmeier, Enno Klussmann
The A-kinase anchoring protein (AKAP) GSK3β interaction protein (GSKIP) is a cytosolic scaffolding protein binding protein kinase A (PKA) and glycogen synthase kinase 3β (GSK3β). Here we show that both the AKAP function of GSKIP, i.e. its direct interaction with PKA, and its direct interaction with GSK3β are required for the regulation of β-catenin and thus Wnt signaling. A cytoplasmic destruction complex targets β-catenin for degradation and thus prevents Wnt signaling. Wnt signals cause β-catenin accumulation and translocation into the nucleus, where it induces Wnt target gene expression...
September 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27375620/molecular-mechanisms-for-camp-mediated-immunoregulation-in-t-cells-role-of-anchored-protein-kinase-a-signaling-units
#15
REVIEW
Vanessa L Wehbi, Kjetil Taskén
The cyclic AMP/protein kinase A (cAMP/PKA) pathway is one of the most common and versatile signal pathways in eukaryotic cells. A-kinase anchoring proteins (AKAPs) target PKA to specific substrates and distinct subcellular compartments providing spatial and temporal specificity for mediation of biological effects channeled through the cAMP/PKA pathway. In the immune system, cAMP is a potent negative regulator of T cell receptor-mediated activation of effector T cells (Teff) acting through a proximal PKA/Csk/Lck pathway anchored via a scaffold consisting of the AKAP Ezrin holding PKA, the linker protein EBP50, and the anchoring protein phosphoprotein associated with glycosphingolipid-enriched microdomains holding Csk...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27357676/gpr161-anchoring-of-pka-consolidates-gpcr-and-camp-signaling
#16
Verena A Bachmann, Johanna E Mayrhofer, Ronit Ilouz, Philipp Tschaikner, Philipp Raffeiner, Ruth Röck, Mathieu Courcelles, Federico Apelt, Tsan-Wen Lu, George S Baillie, Pierre Thibault, Pia Aanstad, Ulrich Stelzl, Susan S Taylor, Eduard Stefan
Scaffolding proteins organize the information flow from activated G protein-coupled receptors (GPCRs) to intracellular effector cascades both spatially and temporally. By this means, signaling scaffolds, such as A-kinase anchoring proteins (AKAPs), compartmentalize kinase activity and ensure substrate selectivity. Using a phosphoproteomics approach we identified a physical and functional connection between protein kinase A (PKA) and Gpr161 (an orphan GPCR) signaling. We show that Gpr161 functions as a selective high-affinity AKAP for type I PKA regulatory subunits (RI)...
July 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27305962/rapid-effects-of-aldosterone-in-primary-cultures-of-cardiomyocytes-do-they-suggest-the-existence-of-a-membrane-bound-receptor
#17
Carolina Morais Araujo, Milla Marques Hermidorff, Gabriela de Cassia Sousa Amancio, Denise da Silveira Lemos, Marcelo Estáquio Silva, Leonardo Vinícius Monteiro de Assis, Mauro César Isoldi
Aldosterone acts on its target tissue through a classical mechanism or through the rapid pathway through a putative membrane-bound receptor. Our goal here was to better understand the molecular and biochemical rapid mechanisms responsible for aldosterone-induced cardiomyocyte hypertrophy. We have evaluated the hypertrophic process through the levels of ANP, which was confirmed by the analysis of the superficial area of cardiomyocytes. Aldosterone increased the levels of ANP and the cellular area of the cardiomyocytes; spironolactone reduced the aldosterone-increased ANP level and cellular area of cardiomyocytes...
October 2016: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/27162341/enhancement-of-%C3%AE-catenin-activity-by-big1-plus-big2-via-arf-activation-and-camp-signals
#18
Chun-Chun Li, Kang Le, Jiro Kato, Joel Moss, Martha Vaughan
Multifunctional β-catenin, with critical roles in both cell-cell adhesion and Wnt-signaling pathways, was among HeLa cell proteins coimmunoprecipitated by antibodies against brefeldin A-inhibited guanine nucleotide-exchange factors 1 and 2 (BIG1 or BIG2) that activate ADP-ribosylation factors (Arfs) by accelerating the replacement of bound GDP with GTP. BIG proteins also contain A-kinase anchoring protein (AKAP) sequences that can act as scaffolds for multimolecular assemblies that facilitate and limit cAMP signaling temporally and spatially...
May 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27148411/expression-and-clinical-significance-of-a-kinase-anchor-protein-4-in-lung-adenocarcinoma-tissue
#19
Hong-Mei Li, Kang Guo, Xiao-Yun Yu, Zhuang Yu, Ping Xu
BACKGROUND: The A-kinase anchor proteins (AKAP) are a growing family of scaffolding proteins involved in the occurrence, proliferation, and metastasis of tumors by controlling intracellular signals. In this study, the expression and significance of AKAP4 were analyzed in patients with lung adenocarcinoma and adjacent non-cancerous tissues. METHODS: Using reverse transcriptase-polymerase chain reaction and Western blot, AKAP4 messenger ribonucleic acid (mRNA) and protein expression levels were measured in 108 cases of lung adenocarcinoma and adjacent non-cancerous tissues...
April 26, 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/27137912/functional-and-structural-mimicry-of-cellular-protein-kinase-a-anchoring-proteins-by-a-viral-oncoprotein
#20
Cason R King, Michael J Cohen, Gregory J Fonseca, Brennan S Dirk, Jimmy D Dikeakos, Joe S Mymryk
The oncoproteins of the small DNA tumor viruses interact with a plethora of cellular regulators to commandeer control of the infected cell. During infection, adenovirus E1A deregulates cAMP signalling and repurposes it for activation of viral gene expression. We show that E1A structurally and functionally mimics a cellular A-kinase anchoring protein (AKAP). E1A interacts with and relocalizes protein kinase A (PKA) to the nucleus, likely to virus replication centres, via an interaction with the regulatory subunits of PKA...
May 2016: PLoS Pathogens
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