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https://www.readbyqxmd.com/read/29743299/the-akap-cypher-zasp-contributes-to-%C3%AE-adrenergic-pka-stimulation-of-cardiac-ca-v-1-2-calcium-channels
#1
Haijie Yu, Can Yuan, Ruth E Westenbroek, William A Catterall
Stimulation of the L-type Ca2+ current conducted by CaV 1.2 channels in cardiac myocytes by the β-adrenergic/protein kinase A (PKA) signaling pathway requires anchoring of PKA to the CaV 1.2 channel by an A-kinase anchoring protein (AKAP). However, the AKAP(s) responsible for regulation in vivo remain unknown. Here, we test the role of the AKAP Cypher/Zasp in β-adrenergic regulation of CaV 1.2 channels using physiological studies of cardiac ventricular myocytes from young-adult mice lacking the long form of Cypher/Zasp (LCyphKO mice)...
May 9, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29717226/aldosterone-impairs-mitochondrial-function-in-human-cardiac-fibroblasts-via-a-kinase-anchor-protein-12
#2
Jaime Ibarrola, Rafael Sadaba, Ernesto Martinez-Martinez, Amaia Garcia-Peña, Vanessa Arrieta, Virginia Alvarez, Amaya Fernández-Celis, Alicia Gainza, Victoria Cachofeiro, Enrique Santamaria, Joaquin Fernandez-Irigoyen, Frederic Jaisser, Natalia Lopez-Andres
Aldosterone (Aldo) contributes to mitochondrial dysfunction and cardiac oxidative stress. Using a proteomic approach, A-kinase anchor protein (AKAP)-12 has been identified as a down-regulated protein by Aldo in human cardiac fibroblasts. We aim to characterize whether AKAP-12 down-regulation could be a deleterious mechanism which induces mitochondrial dysfunction and oxidative stress in cardiac cells. Aldo down-regulated AKAP-12 via its mineralocorticoid receptor, increased oxidative stress and induced mitochondrial dysfunction characterized by decreased mitochondrial-DNA and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expressions in human cardiac fibroblasts...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29700114/disruption-of-protein-kinase-a-localization-induces-acrosomal-exocytosis-in-capacitated-mouse-sperm
#3
Cintia Stival, Carla Ritagliati, Xinran Xu, Maria G Gervasi, Guillermina M Luque, Carolina Baro Graf, José Luis Vega-Beltran, Nicolás I Torres, Alberto Darszon, Diego Krapf, Mariano G Buffone, Pablo Visconti, Dario Krapf
Protein kinase A (PKA) is a broad-spectrum Ser/Thr kinase involved in the regulation of several cellular activities. Thus, its precise activation relies on being localized at specific subcellular places known as discrete PKA signalosomes. A-Kinase Anchoring Proteins (AKAPs) form scaffolding assemblies that play a pivotal role on PKA regulation by restricting its activity to specific micro-domains. Since one of the first signaling events observed during mammalian sperm capacitation is PKA activation, understanding how PKA activity is restricted in space and time is crucial to decipher the critical steps of sperm capacitation...
April 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29688805/opa1-anchored-pka-phosphorylates-perilipin-1-on-s522-and-s497-in-adipocytes-differentiated-from-human-adipose-stem-cells
#4
Marie Rogne, Dinh-Toi Chu, Thomas M Küntziger, Maria-Niki Mylonakou, Philippe Collas, Kjetil Tasken
Optic atrophy 1 (OPA1) is the A-kinase anchoring protein (AKAP) targeting the pool of PKA responsible for perilipin 1 phosphorylation, a gatekeeper for lipolysis. However, the involvement of OPA1-bound PKA in the downstream regulation of lipolysis is unknown. Here, we show upregulation and relocation of OPA1 from mitochondria to lipid droplets during adipocytic differentiation of human adipose stem cells (hASCs). We employed various biochemical and immunological approaches to demonstrate that OPA1-bound PKA phosphorylates perilipin 1 at S522 and S497 upon lipolytic stimulation...
April 24, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29673970/the-role-of-compartmentalized-signaling-pathways-in-the-control-of-mitochondrial-activities-in-cancer-cells
#5
REVIEW
Laura Rinaldi, Rossella Delle Donne, Domenica Borzacchiello, Luigi Insabato, Antonio Feliciello
Mitochondria are the powerhouse organelles present in all eukaryotic cells. They play a fundamental role in cell respiration, survival and metabolism. Stimulation of G-protein coupled receptors (GPCRs) by dedicated ligands and consequent activation of the cAMP·PKA pathway finely coupleenergy production and metabolism to cell growth and survival. Compartmentalization of PKA signaling at mitochondria by A-Kinase Anchor Proteins (AKAPs) ensures efficient transduction of signals generated at the cell membrane to the organelles, controlling important aspects of mitochondrial biology...
April 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29650969/akaps-pka-disruptors-increase-aqp2-activity-independently-of-vasopressin-in-a-model-of-nephrogenic-diabetes-insipidus
#6
Fumiaki Ando, Shuichi Mori, Naofumi Yui, Tetsuji Morimoto, Naohiro Nomura, Eisei Sohara, Tatemitsu Rai, Sei Sasaki, Yoshiaki Kondo, Hiroyuki Kagechika, Shinichi Uchida
Congenital nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine. Congenital NDI is mainly caused by loss-of-function mutations in the vasopressin type 2 receptor (V2R), leading to impaired aquaporin-2 (AQP2) water channel activity. So far, treatment options of congenital NDI either by rescuing mutant V2R with chemical chaperones or by elevating cyclic adenosine monophosphate (cAMP) levels have failed to yield effective therapies. Here we show that inhibition of A-kinase anchoring proteins (AKAPs) binding to PKA increases PKA activity and activates AQP2 channels in cortical collecting duct cells...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29600899/human-muscle-specific-a-kinase-anchoring-protein-makap-polymorphisms-modulate-the-susceptibility-to-cardiovascular-diseases-by-altering-camp-pka-signaling
#7
Santosh V Suryavanshi, Shweta M Jadhav, Kody L Anderson, Panagiotis Katsonis, Olivier Lichtarge, Bradley K McConnell
One of the crucial cardiac signaling pathways is cAMP-mediated PKA signal transduction which is regulated by a family of scaffolding proteins, A-kinase anchoring proteins (AKAPs). Muscle-specific AKAP (mAKAP) partly regulates cardiac cAMP/PKA signaling by binding to PKA and phosphodiesterase4D3 (PDE4D3) among other proteins and plays a central role in modulating cardiac remodeling. Moreover, genetics plays an incomparable role in modifying the risk of cardiovascular diseases (CVDs). Especially, single nucleotide polymorphisms (SNPs) in various proteins have been shown to predispose individuals to CVDs...
March 30, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29599290/tgf%C3%AE-and-igf1r-signaling-activate-protein-kinase-a-through-differential-regulation-of-ezrin-phosphorylation-in-colon-cancer-cells
#8
Premila D Leiphrakpam, Michael G Brattain, Jennifer D Black, Jenny Jing Wang
Aberrant cell survival plays a critical role in cancer progression and metastasis. We have previously shown that ezrin, a cAMP-dependent A-kinase anchoring protein (AKAP), is upregulated in colorectal cancer (CRC) liver metastasis. Phosphorylation of ezrin at threonine 567(T567) activates ezrin and plays an important role in CRC cell survival associated with XIAP and survivin upregulation. In this study, we demonstrate that, in FET and GEO colon cancer cells, knockdown of ezrin expression or inhibition of ezrin phosphorylation at T567 increases apoptosis through PKA activation in a cAMP-independent manner...
March 29, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29461511/roles-of-a-kinase-anchoring-proteins-and-phosphodiesterases-in-the-cardiovascular-system
#9
REVIEW
Maria Ercu, Enno Klussmann
A-kinase anchoring proteins (AKAPs) and cyclic nucleotide phosphodiesterases (PDEs) are essential enzymes in the cyclic adenosine 3'-5' monophosphate (cAMP) signaling cascade. They establish local cAMP pools by controlling the intensity, duration and compartmentalization of cyclic nucleotide-dependent signaling. Various members of the AKAP and PDE families are expressed in the cardiovascular system and direct important processes maintaining homeostatic functioning of the heart and vasculature, e.g., the endothelial barrier function and excitation-contraction coupling...
February 20, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29449124/investigating-pka-rii-specificity-using-analogs-of-the-pka-akap-peptide-inhibitor-stad-2
#10
N George Bendzunas, Sabrina Dörfler, Karolin Autenrieth, Daniela Bertinetti, Erik M F Machal, Eileen J Kennedy, Friedrich W Herberg
Generation of the second messenger molecule cAMP mediates a variety of cellular responses which are essential for critical cellular processes. In response to elevated cAMP levels, cAMP dependent protein kinase (PKA) phosphorylates serine and threonine residues on a wide variety of target substrates. In order to enhance the precision and directionality of these signaling events, PKA is localized to discrete locations within the cell by A-kinase anchoring proteins (AKAPs). The interaction between PKA and AKAPs is mediated via an amphipathic α-helix derived from AKAPs which binds to a stable hydrophobic groove formed in the dimerization/docking (D/D) domain of PKA-R in an isoform-specific fashion...
March 15, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29433456/exome-sequencing-of-primary-breast-cancers-with-paired-metastatic-lesions-reveals-metastasis-enriched-mutations-in-the-a-kinase-anchoring-protein-family-akaps
#11
Una Kjällquist, Rikard Erlandsson, Nicholas P Tobin, Amjad Alkodsi, Ikram Ullah, Gustav Stålhammar, Eva Karlsson, Thomas Hatschek, Johan Hartman, Sten Linnarsson, Jonas Bergh
BACKGROUND: Tumor heterogeneity in breast cancer tumors is today widely recognized. Most of the available knowledge in genetic variation however, relates to the primary tumor while metastatic lesions are much less studied. Many studies have revealed marked alterations of standard prognostic and predictive factors during tumor progression. Characterization of paired primary- and metastatic tissues should therefore be fundamental in order to understand mechanisms of tumor progression, clonal relationship to tumor evolution as well as the therapeutic aspects of systemic disease...
February 12, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29419761/a-kinase-anchoring-protein-lbc-a-molecular-scaffold-involved-in-cardiac-protection
#12
REVIEW
Dario Diviani, Halima Osman, Erica Reggi
Heart failure is a lethal disease that can develop after myocardial infarction, hypertension, or anticancer therapy. In the damaged heart, loss of function is mainly due to cardiomyocyte death and associated cardiac remodeling and fibrosis. In this context, A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins that facilitate the spatiotemporal activation of the cyclic adenosine monophosphate (AMP)-dependent protein kinase (PKA) and other transduction enzymes involved in cardiac remodeling...
February 8, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29388469/akap1-genetic-deletion-increases-the-severity-of-hyperoxia-induced-acute-lung-injury-in-mice
#13
Venkata R Narala, Jutaro Fukumoto, Helena Hernández-Cuervo, Sahebgowda Sidramagowda Patil, Sudarshan Krishnamurthy, Mason Breitzig, Lakshmi Galam, Ramani Soundararajan, Richard F Lockey, Narasaiah Kolliputi
Critically ill patients are commonly treated with high levels of oxygen, hyperoxia, for prolonged periods of time. Unfortunately, extended exposure to hyperoxia can exacerbate respiratory failure and lead to a high mortality rate. Mitochondrial A-kinase anchoring protein (Akap) has been shown to regulate mitochondrial function. It has been reported that, under hypoxic conditions, Akap121 undergoes proteolytic degradation and promotes cardiac injury. However, the role of Akap1 in hyperoxia-induced acute lung injury (ALI) is largely unknown...
February 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29385021/pde4-mediated-camp-signalling
#14
REVIEW
Bracy A Fertig, George S Baillie
cAMP is the archetypal and ubiquitous second messenger utilised for the fine control of many cardiovascular cell signalling systems. The ability of cAMP to elicit cell surface receptor-specific responses relies on its compartmentalisation by cAMP hydrolysing enzymes known as phosphodiesterases. One family of these enzymes, PDE4, is particularly important in the cardiovascular system, where it has been extensively studied and shown to orchestrate complex, localised signalling that underpins many crucial functions of the heart...
January 31, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29373579/an-akap-lbc-rhoa-interaction-inhibitor-promotes-the-translocation-of-aquaporin-2-to-the-plasma-membrane-of-renal-collecting-duct-principal-cells
#15
Katharina Schrade, Jessica Tröger, Adeeb Eldahshan, Kerstin Zühlke, Kamal R Abdul Azeez, Jonathan M Elkins, Martin Neuenschwander, Andreas Oder, Mohamed Elkewedi, Sarah Jaksch, Karsten Andrae, Jinliang Li, Joao Fernandes, Paul Markus Müller, Stephan Grunwald, Stephen F Marino, Tanja Vukićević, Jenny Eichhorst, Burkhard Wiesner, Marcus Weber, Michael Kapiloff, Oliver Rocks, Oliver Daumke, Thomas Wieland, Stefan Knapp, Jens Peter von Kries, Enno Klussmann
Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29370121/polymorphisms-mutations-in-a-kinase-anchoring-proteins-akaps-role-in-the-cardiovascular-system
#16
REVIEW
Santosh V Suryavanshi, Shweta M Jadhav, Bradley K McConnell
A-kinase anchoring proteins (AKAPs) belong to a family of scaffolding proteins that bind to protein kinase A (PKA) by definition and a variety of crucial proteins, including kinases, phosphatases, and phosphodiesterases. By scaffolding these proteins together, AKAPs build a "signalosome" at specific subcellular locations and compartmentalize PKA signaling. Thus, AKAPs are important for signal transduction after upstream activation of receptors ensuring accuracy and precision of intracellular PKA-dependent signaling pathways...
January 25, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29367580/function-of-adenylyl-cyclase-in-heart-the-akap-connection
#17
REVIEW
Tanya A Baldwin, Carmen W Dessauer
Cyclic adenosine monophosphate (cAMP), synthesized by adenylyl cyclase (AC), is a universal second messenger that regulates various aspects of cardiac physiology from contraction rate to the initiation of cardioprotective stress response pathways. Local pools of cAMP are maintained by macromolecular complexes formed by A-kinase anchoring proteins (AKAPs). AKAPs facilitate control by bringing together regulators of the cAMP pathway including G-protein-coupled receptors, ACs, and downstream effectors of cAMP to finely tune signaling...
January 16, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29367252/mimicry-of-cellular-a-kinase-anchoring-proteins-is-a-conserved-and-critical-function-of-e1a-across-various-human-adenovirus-species
#18
Cason R King, Steven F Gameiro, Tanner M Tessier, Ali Zhang, Joe S Mymryk
The E1A proteins of the various human adenovirus (HAdV) species perform the critical task of converting an infected cell into a setting primed for virus replication. While E1A proteins differ in both sequence and mechanism, the evolutionary pressure on viruses with limited coding capacity ensures that these proteins often have significant overlap in critical functions. HAdV-5 E1A is known to use mimicry to rewire cyclic AMP (cAMP) signaling by decoupling protein kinase A (PKA) from cellular A-kinase anchoring proteins (AKAPs) and utilizing PKA to its own advantage...
January 24, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317777/a-kinase-anchoring-protein-150-akap150-promotes-cocaine-reinstatement-by-increasing-ampa-receptor-transmission-in-the-accumbens-shell
#19
Leonardo A Guercio, Mackenzie E Hofmann, Sarah E Swinford-Jackson, Julia S Sigman, Mathieu E Wimmer, Mark L Dell'Acqua, Heath D Schmidt, R Christopher Pierce
Previous work indicated that activation of D1-like dopamine receptors (D1DRs) in the nucleus accumbens shell promoted cocaine seeking through a process involving the activation of PKA and GluA1-containing AMPA receptors (AMPARs). A-kinase anchoring proteins (AKAPs) localize PKA to AMPARs leading to enhanced phosphorylation of GluA1. AKAP150, the most well-characterized isoform, plays an important role in several forms of neuronal plasticity. However, its involvement in drug addiction has been minimally explored...
December 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29288530/pka-binding-domain-of-akap8-is-essential-for-direct-interaction-with-dpy30-protein
#20
Anna Bieluszewska, Martyna Weglewska, Tomasz Bieluszewski, Krzysztof Lesniewicz, Elzbieta Poreba
The main function of the A kinase-anchoring proteins (AKAPs) is to target the cyclic AMP-dependent protein kinase A (PKA) to its cellular substrates through the interaction with its regulatory subunits. Besides anchoring of PKA, AKAP8 participates in regulating the histone H3 lysine 4 (H3K4) histone methyltransferase (HMT) complexes. It is also involved in DNA replication, apoptosis, transcriptional silencing of rRNA genes, alternative splicing, and chromatin condensation during mitosis. In this study, we focused on the interaction between AKAP8 and the core subunit of all known H3K4 HMT complexes-DPY30 protein...
March 2018: FEBS Journal
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