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J O Machuki, H Y Zhang, S E Harding, H Sun
Oestrogen receptors (ERs) and β-adrenergic receptors (βARs) play important roles in the cardiovascular system. Moreover, these receptors are expressed in cardiac myocytes and vascular tissues. Numerous experimental observations support the hypothesis that similarities and interactions exist between the signalling pathways of ERs (ERα, ERβ and GPR30) and βARs (β1 AR, β2 AR and β3 AR). The recently discovered oestrogen receptor GPR30 shares structural features with the βARs, and this forms the basis for the interactions and functional overlap...
October 9, 2017: Acta Physiologica
Wang Cong, Xianglian Meng, Jin Li, Qiushi Zhang, Feng Chen, Wenjie Liu, Ying Wang, Sipu Cheng, Xiaohui Yao, Jingwen Yan, Sungeun Kim, Andrew J Saykin, Hong Liang, Li Shen
BACKGROUND: The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ1-42 are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks...
May 30, 2017: BMC Genomics
Ernesto Gonzalez de Valdivia, Stefan Broselid, Robin Kahn, Björn Olde, L M Fredrik Leeb-Lundberg
G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen receptor 1 (GPER1), is thought to play important roles in breast cancer and cardiometabolic regulation, but many questions remain about ligand activation, effector coupling, and subcellular localization. We showed recently that GPR30 interacts through the C-terminal type I PDZ motif with SAP97 and protein kinase A (PKA)-anchoring protein (AKAP) 5, which anchor the receptor in the plasma membrane and mediate an apparently constitutive decrease in cAMP production independently of Gi/o Here, we show that GPR30 also constitutively increases ERK1/2 activity...
June 16, 2017: Journal of Biological Chemistry
Chong Han, Hirofumi Tomita, Takayoshi Ohba, Kimitaka Nishizaki, Yoshiki Ogata, Yasushi Matsuzaki, Daisuke Sawamura, Teruyuki Yanagisawa, Tomohiro Osanai, Tadaatsu Imaizumi, Atsushi Matsubara, Takeshi Adachi, Kyoichi Ono, Ken Okumura, Manabu Murakami
Genetic analyses have revealed an important association between A-kinase anchoring proteins (AKAPs) and the intracellular calcium modulating system. AKAP5, also known as AKAP79/150, is an anchoring protein between PKA and voltage-dependent calcium channels, ryanodine receptor-2, phospholamban and other molecules. The aim of the present study was to elucidate the physiological importance of AKAP5 in the creation of cardiac rhythm using AKAP5-null mice. ECG analysis showed a normal sinus rhythm and a decreased responsiveness to isoproterenol in AKAP5-null mice compared with wild-type mice...
January 22, 2016: Biochemical and Biophysical Research Communications
Yanjing Guo, Tao Bo, Xinli Zhou, Ling Gao, Yong Wang, Jiajun Zhao
Kinase Anchoring Proteins (AKAPs) have evolved to regulate the spatial and temporal organization of cellular signal transduction. As a typical member, AKAP5 which consisting of three orthologues: bovine AKAP75, rodent AKAP150 and human AKAP79, is the best known model in the anchoring and targeting properties. It is shown that AKAP5 can bind β2-adrenergic receptor, which is a member of GPCR superfamily, and orchestrate the interactions of various protein kinases, protein phosphatases and cytoskeletal element...
2015: Neuro Endocrinology Letters
Wilfred J Poppinga, Irene H Heijink, Laura J Holtzer, Philipp Skroblin, Enno Klussmann, Andrew J Halayko, Wim Timens, Harm Maarsingh, Martina Schmidt
β2-Agonist inhibitors can relieve chronic obstructive pulmonary disease (COPD) symptoms by stimulating cyclic AMP (cAMP) signaling. A-kinase-anchoring proteins (AKAPs) compartmentalize cAMP signaling by establishing protein complexes. We previously reported that the β2-agonist fenoterol, direct activation of protein kinase A (PKA), and exchange factor directly activated by cAMP decrease cigarette smoke extract (CSE)-induced release of neutrophil attractant interleukin-8 (IL-8) from human airway smooth muscle (ASM) cells...
April 15, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Graham H Diering, Ahleah S Gustina, Richard L Huganir
Bidirectional synaptic plasticity occurs locally at individual synapses during long-term potentiation (LTP) or long-term depression (LTD), or globally during homeostatic scaling. LTP, LTD, and homeostatic scaling alter synaptic strength through changes in postsynaptic AMPA-type glutamate receptors (AMPARs), suggesting the existence of overlapping molecular mechanisms. Phosphorylation controls AMPAR trafficking during LTP/LTD. We addressed the role of AMPAR phosphorylation during homeostatic scaling. We observed bidirectional changes of the levels of phosphorylated GluA1 S845 during scaling, resulting from a loss of protein kinase A (PKA) from synapses during scaling down and enhanced activity of PKA in synapses during scaling up...
November 19, 2014: Neuron
Xin Li, Shannon M Matta, Ryan D Sullivan, Suleiman W Bahouth
AIMS: Cardiac β-adrenergic receptors (β-AR) are key regulators of cardiac haemodynamics and size. The scaffolding protein A-kinase anchoring protein 79/150 (AKAP5) is a key regulator of myocardial signalling by β-ARs. We examined the function of AKAP5 in regulating cardiac haemodynamics and size, and the role of β-ARs and Ca(2+)-regulated intracellular signalling pathways in this phenomenon. METHODS AND RESULTS: We used echocardiographic, histological, genetic, and biochemical methods to examine the effect of ablation of AKAP5 on cardiac haemodynamics, size, and signalling in mice...
November 1, 2014: Cardiovascular Research
W J Poppinga, P Muñoz-Llancao, C González-Billault, M Schmidt
The universal second messenger cAMP is generated upon stimulation of Gs protein-coupled receptors, such as the β2 -adreneoceptor, and leads to the activation of PKA, the major cAMP effector protein. PKA oscillates between an on and off state and thereby regulates a plethora of distinct biological responses. The broad activation pattern of PKA and its contribution to several distinct cellular functions lead to the introduction of the concept of compartmentalization of cAMP. A-kinase anchoring proteins (AKAPs) are of central importance due to their unique ability to directly and/or indirectly interact with proteins that either determine the cellular content of cAMP, such as β2 -adrenoceptors, ACs and PDEs, or are regulated by cAMP such as the exchange protein directly activated by cAMP...
December 2014: British Journal of Pharmacology
Stefan Broselid, Kelly A Berg, Teresa A Chavera, Robin Kahn, William P Clarke, Björn Olde, L M Fredrik Leeb-Lundberg
GPR30, or G protein-coupled estrogen receptor, is a G protein-coupled receptor reported to bind 17β-estradiol (E2), couple to the G proteins Gs and Gi/o, and mediate non-genomic estrogenic responses. However, controversies exist regarding the receptor pharmacological profile, effector coupling, and subcellular localization. We addressed the role of the type I PDZ motif at the receptor C terminus in receptor trafficking and coupling to cAMP production in HEK293 cells and CHO cells ectopically expressing the receptor and in Madin-Darby canine kidney cells expressing the native receptor...
August 8, 2014: Journal of Biological Chemistry
Manuel F Navedo, Johannes W Hell
In this issue of Cell Reports, Murphy et al. and Dittmer et al. present exciting new insight into the regulation of Ca2+ influx via the L-type Ca2+ channel Cav1.2 and how increased Ca2+ influx translates into localized activation of the nuclear transcription factor NFAT upon depolarization in neurons.
June 12, 2014: Cell Reports
Chunlei Han, Fangang Meng, Jian Pan, Ali Liu, Kai Zhang, Jianguo Zhang
OBJECTIVE: To explore the core controlling genes and their functions and pathways of gamma knife in the treatment of epilepsy in rats. METHODS: The temporal epilepsy rats induced by stereotactic technique were irradiated with gamma knife. Total RNA samples were isolated at 3 weeks post-irradiation. After hybridization, washing and staining, the probe arrays were scanned to acquire the gene chip data. The functional categories and affected pathways of differentially regulated genes were analyzed...
January 7, 2014: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Linghai Yang, Merle L Gilbert, Ruimao Zheng, G Stanley McKnight
Striatal medium spiny neurons (MSNs) mediate many of the physiological effects of dopamine, including the regulation of feeding and motor behaviors. Dopaminergic inputs from the midbrain modulate MSN excitability through pathways that involve cAMP and protein kinase A (PKA), but the physiological role of specific PKA isoforms in MSN neurons remains poorly understood. One of the major PKA regulatory (R) subunit isoforms expressed in MSNs is RIIβ, which localizes the PKA holoenzyme primarily to dendrites by interaction with AKAP5 and other scaffolding proteins...
April 2, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Daphné Lehalle, Damien Sanlaville, Anne Guimier, Emmanuel Plouvier, Thierry Leblanc, Louise Galmiche, Isabelle Radford, Serge Romana, Laurence Colleaux, Loïc de Pontual, Stanislas Lyonnet, Jeanne Amiel
Neuroblastoma is the most frequent extra cranial solid tumor in infants and children. Genetic predisposition to neuroblastoma has been suspected previously due to familial cases of sporadic NB and predisposition to NB in several syndromes. Here, we report on a de novo 14q23.1-q23.3 microdeletion in a male presenting with a neuroblastoma diagnosed at 9 months, and spherocytosis, congenital heart defect, cryptorchidism, hypoplasia of corpus callosum, epilepsy, and developmental delay. Myc-associated-factor X (MAX) haploinsufficiency could be regarded as the predisposing factor to NB...
May 2014: American Journal of Medical Genetics. Part A
Lei Jiang, Zhao Dong, Fengpeng Li, Ruozhuo Liu, Enchao Qiu, Xiaolin Wang, Shengyuan Yu
BACKGROUND: The molecular and cellular origins of migraine headache are among the most complex problems in contemporary neurology. Up to now the pathogenesis of migraine still remains unclearly defined. The objective of this study was to explore new factors that may be related to the mechanism of migraine. METHODS: The present study performed a comprehensive analysis of gene expression in the trigeminal nucleus caudalis induced by electrical stimulation of dura mater surrounding the superior sagittal sinus in conscious rats using microarray analysis followed by quantitative real-time reverse-transcribed polymerase chain reaction (qRT-PCR) verification...
2014: Chinese Medical Journal
Takanori Nishimura, Wataru Fujii, Koji Sugiura, Kunihiko Naito
Mammalian growing oocytes (GOs) lack the ability to resume meiosis, although the molecular mechanism of this limitation is not fully understood. We previously hypothesized that the meiotic incompetence of porcine GOs was attributed to complex spatial-temporal regulation of cAMP-dependent protein kinase (PKA) by A-kinase anchor proteins (AKAPs), but found that AKAP1 is not involved in the meiotic incompetence of porcine GOs. In the present study, we cloned porcine cDNAs of AKAP5 and AKAP7alpha, and found that inhibiting the expression of these AKAPs induced PKA translocation into the nucleus and promoted meiotic resumption of porcine GOs without affecting the total PKA activity of GOs, whereas overexpressing these AKAPs had no effect...
March 2014: Biology of Reproduction
Anouk Oldenburger, Wilfred J Poppinga, Fleur Kos, Harold G de Bruin, Wolter F Rijks, Irene H Heijink, Wim Timens, Herman Meurs, Harm Maarsingh, Martina Schmidt
Airway epithelium, which forms the first barrier towards environmental insults, is disturbed by cigarette smoking, a major risk factor for developing chronic obstructive pulmonary disease (COPD). A-kinase anchoring proteins (AKAP) maintain endothelial barrier function and coordinate subcellular localization of protein kinase A (PKA). However, the role of AKAPs in epithelial barrier function is unknown. We studied the role of AKAPs in regulating human bronchial epithelial (Hogg JC, Timens W. Annu Rev Pathol 4: 435-459, 2009; HBE) barrier...
March 15, 2014: American Journal of Physiology. Cell Physiology
Xin Li, Mohammed M Nooh, Suleiman W Bahouth
Protein kinase A-anchoring proteins (AKAPs) participate in the formation of macromolecular signaling complexes that include protein kinases, ion channels, effector enzymes, and G-protein-coupled receptors. We examined the role of AKAP79/150 (AKAP5) in trafficking and signaling of the β1-adrenergic receptor (β1-AR). shRNA-mediated down-regulation of AKAP5 in HEK-293 cells inhibited the recycling of the β1-AR. Recycling of the β1-AR in AKAP5 knockdown cells was rescued by shRNA-resistant AKAP5. However, truncated mutants of AKAP5 with deletions in the domains involved in membrane targeting or in binding to calcineurin or PKA failed to restore the recycling of the β1-AR, indicating that full-length AKAP5 was required...
November 22, 2013: Journal of Biological Chemistry
Mingxu Zhang, Tommaso Patriarchi, Ivar S Stein, Hai Qian, Lucas Matt, Minh Nguyen, Yang K Xiang, Johannes W Hell
Recent evidence indicates that the A kinase anchor protein AKAP5 (AKAP79/150) interacts not only with PKA but also with various adenylyl cyclase (AC) isoforms. However, the physiological relevance of AC-AKAP5 binding is largely unexplored. We now show that postsynaptic targeting of AC by AKAP5 is important for phosphorylation of the AMPA-type glutamate receptor subunit GluA1 on Ser-845 by PKA and for synaptic plasticity. Phosphorylation of GluA1 on Ser-845 is strongly reduced (by 70%) under basal conditions in AKAP5 KO mice but not at all in D36 mice, in which the PKA binding site of AKAP5 (i...
June 14, 2013: Journal of Biological Chemistry
Hans-Gert Bernstein, Henrik Dobrowolny, Björn H Schott, Xenia Gorny, Veronika Becker, Johann Steiner, Constanze I Seidenbecher, Bernhard Bogerts
Brain anatomical abnormalities as well as cognitive and emotional processing deficits have been reported for the prefrontal cortex in bipolar disorder, which are in part attributable to cellular and laminar abnormalities in postsynaptic protein expression. A kinase anchoring protein (AKAP) 5/79 plays a key role in postsynaptic signalling of excitatory synapses. We aimed to reveal if the cellular expression of AKAP5/79 protein is altered in the anterior cingulate cortex and the dorsolateral prefrontal cortex in bipolar disorder...
June 2013: Journal of Psychiatric Research
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