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Calcium dependent protein kinase

Juan J Ferreira, Alice Butler, Richard Stewart, Ana Laura Gonzalez-Cota, Pascale Lybaert, Chinwendu Amazu, Erin L Reinl, Monali Wakle-Prabagaran, Lawrence Salkoff, Sarah K England, Celia M Santi
KEY POINTS: At the end of pregnancy, the uterus transitions from a quiescent state to a highly contractile state. This transition requires that the uterine (myometrial) smooth muscle cells increase their excitability, but how this occurs is not fully understood. We identified SLO2.1, a potassium channel heretofore unknown to be in uterine smooth muscle as a potential significant contributor to the electrical excitability of myometrial smooth muscle cells. We found that activity of the SLO2...
October 17, 2018: Journal of Physiology
Megan B Miller, Rashaun S Wilson, TuKiet T Lam, Angus C Nairn, Marina R Picciotto
Activation of nicotinic acetylcholine receptors containing α4 and β2 subunits (α4/β2* nAChRs) in the mammalian brain is necessary for nicotine reinforcement and addiction. We previously identified interactions between α4/β2* nAChRs and calcium/calmodulin-dependent protein kinase II (CaMKII) in mouse and human brain tissue. Following co-expression of α4/β2 nAChR subunits with CaMKII in HEK cells, mass spectrometry identified 8 phosphorylation sites in the α4 subunit. One of these sites and an additional site were identified when isolated α4/β2* nAChRs were dephosphorylated and subsequently incubated with CaMKII in vitro, while 3 phosphorylation sites were identified following incubation with protein kinase A (PKA) in vitro...
October 15, 2018: Proteomes
Dana Elbers, Alexander Scholten, Karl-Wilhelm Koch
Primary steps in vertebrate vision occur in rod and cone cells of the retina and require precise molecular switches in excitation, recovery, and adaptation. In particular, recovery of the photoresponse and light adaptation processes are under control of neuronal Ca2+ sensor (NCS) proteins. Among them, the Ca2+ sensor recoverin undergoes a pronounced Ca2+ -dependent conformational change, a prototypical so-called Ca2+ -myristoyl switch, which allows selective targeting of G protein-coupled receptor kinase. Zebrafish ( Danio rerio ) has gained attention as a model organism in vision research...
2018: Frontiers in Molecular Neuroscience
Christopher S Farrar, Denise C Hocking
Cellular responses to platelet-derived growth factor (PDGF) are altered in a variety of pathological conditions, including cancers, fibroses, and vascular diseases, making PDGF-induced signaling pathways important therapeutic targets. The limited success of therapies designed to impact PDGF pathways may be overcome with a clearer understanding of how cells integrate signals from PDGF and the extracellular matrix (ECM). Here, we assessed the effects of fibronectin matrix assembly on the responsiveness of mesenchymal cells to PDGF...
October 15, 2018: Journal of Biological Chemistry
Daniel Markx, Julia Schuhholz, Michael Abadier, Sandra Beier, Mariana Lang, Barbara Moepps
In man, two CC chemokine receptor isoforms, CCR2a and CCR2b, are present that belong to the rhodopsin-like G protein-coupled receptor family, and couple to Gi and Gq family members. The CCR2 receptors are known to regulate canonical functions of chemokines such as directed migration of leukocytes, and to potentially control non-canonical functions such as differentiation, proliferation, and gene transcription of immune and non-immune cells. We recently reported on the activation of phospholipase C isoenzymes and RhoA GTPases by coupling of the two CCR2 receptors to members of the Gq family, in particular Gαq and Gα14 ...
October 12, 2018: Cellular Signalling
Brent M Wood, Mitchell Simon, Samuel Galice, Chidera C Alim, Maura Ferrero, Natalie N Pinna, Donald M Bers, Julie Bossuyt
Calcium-calmodulin dependent protein kinase IIδ (CaMKIIδ) is an important regulator of cardiac electrophysiology, calcium (Ca) balance, contraction, transcription, arrhythmias and progression to heart failure. CaMKII is readily activated at mouths of dyadic cleft Ca channels, but because of its low Ca-calmodulin affinity and presumed immobility it is less clear how CaMKII gets activated near other known, extra-dyad targets. CaMKII is typically considered to be anchored in cardiomyocytes, but while untested, mobility of active CaMKII could provide a mechanism for broader target phosphorylation in cardiomyocytes...
October 12, 2018: Journal of Molecular and Cellular Cardiology
Demetrios A Arvanitis, Elizabeth Vafiadaki, Daniel M Johnson, Evangelia G Kranias, Despina Sanoudou
Sudden unexpected cardiac death (SCD) accounts for up to half of all-cause mortality of heart failure patients. Standardized cardiology tools such as electrocardiography, cardiac imaging, electrophysiological and serum biomarkers cannot accurately predict which patients are at risk of life-threatening arrhythmic episodes. Recently, a common variant of the histidine-rich calcium binding protein (HRC), the Ser96Ala, was identified as a potent biomarker of malignant arrhythmia triggering in these patients. HRC has been shown to be involved in the regulation of cardiac sarcoplasmic reticulum (SR) Ca2+ cycling, by binding and storing Ca2+ in the SR, as well as interacting with the SR Ca2+ uptake and release complexes...
2018: Frontiers in Physiology
Pietro Minuz, Alessandra Meneguzzi, Laura Fumagalli, Maurizio Degan, Stefano Calabria, Roberta Ferraro, Marco Ricci, Dino Veneri, Giorgio Berton
The thromboxane (TX) A2 elicits TP-dependent different platelet responses. Low amounts activate Src kinases and the Rho-Rho kinase pathway independently of integrin αIIb β3 and ADP secretion and synergize with epinephrine to induce aggregation. Aim of the present study was to investigate the role Src kinases and the interplay with calcium signals in reactive oxygen species (ROS) generation in the activatory pathways engaged by TXA2 in human platelets. All the experiments were performed in vitro or ex vivo ...
2018: Frontiers in Pharmacology
Hanwei Fang, Ana Rita Gomes, Natacha Klages, Paco Pino, Bohumil Maco, Eloise M Walker, Zenon A Zenonos, Fiona Angrisano, Jake Baum, Christian Doerig, David A Baker, Oliver Billker, Mathieu Brochet
In malaria parasites, evolution of parasitism has been linked to functional optimisation. Despite this optimisation, most members of a calcium-dependent protein kinase (CDPK) family show genetic redundancy during erythrocytic proliferation. To identify relationships between phospho-signalling pathways, we here screen 294 genetic interactions among protein kinases in Plasmodium berghei. This reveals a synthetic negative interaction between a hypomorphic allele of the protein kinase G (PKG) and CDPK4 to control erythrocyte invasion which is conserved in P...
October 12, 2018: Nature Communications
Alon Amir, Jean-Francois Paré, Yoland Smith, Denis Paré
One of the main subcortical inputs to the basolateral nucleus of the amygdala (BL) originates from a group of dorsal thalamic nuclei located at or near the midline, mainly from the central medial (CMT) and paraventricular (PVT) nuclei. Although similarities between the responsiveness of BL, CMT, and PVT neurons to emotionally arousing stimuli suggest that these thalamic inputs exert a significant influence over BL activity, little is known about the synaptic relationships that mediate these effects. Thus, the present study used Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracing and electron microscopy to shed light on the ultrastructural properties and synaptic targets of CMT and PVT axon terminals in the rat BL...
October 12, 2018: Journal of Comparative Neurology
Marta Toral, Rosario Jimenez, Sebastián Montoro-Molina, Miguel Romero, Rosemary Wangensteen, Juan Duarte, Félix Vargas
Thyroid hormone activity is associated with L-arginine metabolism and nitric oxide (NO) production, which participate in the cardiovascular manifestations of thyroid disorders. L-arginine transporters play an important role in activating L-arginine uptake and NO production. However, the effects of thyroid hormones on L-arginine transporters in endothelial cells have not yet been evaluated. The following methods were used. We measured L-arginine uptake, mRNA expression of L-arginine transporters, endothelial nitric oxide synthase (eNOS) mRNA and NO generation after the administration of T3, T4 and the T3 analog, 3,3′,5-triiodothyroacetic acid TRIAC in human umbilical vein endothelial cells (HUVECs)...
October 1, 2018: Journal of Endocrinology
Mentor Sopjani, Lulzim Millaku, Dashnor Nebija, Merita Emini, Miribane Dermaku-Sopjani, Arleta Rifati-Nixha
Glycogen synthase kinase-3 (GSK-3) is a highly evolutionarily conserved and ubiquitously expressed serine/threonine kinase, an enzyme protein profoundly specific for glycogen synthase (GS). GSK-3 is involved in various cellular functions and physiological processes, including cell proliferation, differentiation, motility, and survival as well as glycogen metabolism, protein synthesis, and apoptosis. There are two isoforms of human GSK-3 (named GSK-3α and GSK-3β) encoded by two distinct genes. Recently, GSK-3β has been reported to function as a powerful regulator of various transport processes across the cell membrane...
October 9, 2018: Current Medicinal Chemistry
Soomin Ryu, Fuller W Bazer, Whasun Lim, Gwonhwa Song
Chrysin is a natural compound derived from honey, propolis, or passion flowers and has many functional roles, such as antiinflammatory and antiangiogenesis effects. Although endometriosis is a benign gynecological disease, there is a need to identify the pathology and develop a therapy for endometriosis. Elucidating the biological mechanism of chrysin on endometriosis will improve the understanding of endometriosis. In this study, we confirmed the apoptotic effects of chrysin in human endometriotic cells using End1/E6E7 (endocervix-derived endometriotic cells) and VK2/E6E7 (vaginal mucosa-derived epithelial endometriotic cells)...
October 9, 2018: Journal of Cellular Physiology
Qiuyu Wang, Chunlin Zhao, Lili Jin, Hanyu Zhang, Qifan Miao, Hongsheng Liu, Dianbao Zhang
Diabetes is a metabolic disorder leading to many complications. The treatment of diabetes mainly depends on hypoglycemic drugs, often with side effects, which drive us to develop novel agents. AWRK6 was a peptide developed from the antimicrobial peptide Dybowskin-2CDYa in our previous study, and the availability of AWRK6 on diabetes intervention was unknown. Here, in vivo and in vitro experiments were carried out to investigate the effects of AWRK6 against diabetes. In diabetic mice, induced by high-fat diet followed by streptozocin (STZ) administration, the daily administration of AWRK6 presented acute and sustained hypoglycemic effects...
October 7, 2018: International Journal of Molecular Sciences
Melissa Bredow, Jacqueline Monaghan
Activation of Ca2+ signaling is a universal response to stress that allows cells to quickly respond to environmental cues. Fluctuations in cytosolic calcium are decoded in plants by calcium-sensing proteins such as Ca2+-dependent protein kinases (CDPKs). The perception of microbes results in an influx of calcium that activates numerous CDPKs that propagate immune signals required for resistance against disease-causing pathogens. This review describes our current understanding of CDPK activation and regulation, and provides a comprehensive overview of CDPK-mediated immune signaling through interaction with various substrates...
October 9, 2018: Molecular Plant-microbe Interactions: MPMI
Erin J Kodis, Sophie Choi, Eric Swanson, Gonzalo Ferreira, George S Bloom
INTRODUCTION: Alzheimer's disease (AD) symptoms reflect synaptic dysfunction and neuron death. Amyloid-β oligomers (AβOs) induce excess calcium entry into neurons via N-methyl-D-aspartate receptors (NMDARs), contributing to synaptic dysfunction. The study described here tested the hypothesis that AβO-stimulated calcium entry also drives neuronal cell cycle reentry (CCR), a prelude to neuron death in AD. METHODS: Pharmacologic modulators of calcium entry and gene expression knockdown were used in cultured neurons and AD model mice...
October 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Xiaowei Ding, Xingzhu Ju, Yan Lu, Wei Chen, Jiaqiang Wang, Changhong Miao, Jiawei Chen
PURPOSE: Angiotensin II (Ang II) has been shown to be involved in neurological disorders. Propofol demonstrated neuroprotective effects in neurons. METHODS: Mouse hippocampal HT22 cells were pre-treated with propofol, followed by Ang II treatment. The expression of synaptic proteins (synapsin I and PSD95) was examined. The effects of propofol on Ang II-induced NADPH oxidase expression and superoxide anion generation were examined. The effects of propofol on intracellular calcium concentration, the activation of calcium/calmodulin-dependent protein kinase II (CaMKII), and protein kinase C (PKC) were measured...
October 6, 2018: Journal of Anesthesia
André da Silva Santiago, Rafael M Couñago, Priscila Zonzini Ramos, Paulo H C Godoi, Katlin B Massirer, Opher Gileadi, Jonathan M Elkins
The calcium/calmodulin-dependent protein kinases (CAMKKs) are upstream activators of CAMK1 and CAMK4 signalling and have important functions in neural development, maintenance and signalling, as well as in other aspects of biology such as Ca2+ signalling in the cardiovascular system. To support the development of specific inhibitors of CAMKKs we have determined the crystal structure of CAMKK1 with two ATP-competitive inhibitors. The structures reveal small but exploitable differences between CAMKK1 and CAMKK2, despite the high sequence identity, which could be used in the generation of specific inhibitors...
October 4, 2018: Scientific Reports
Peter D Yim, George Gallos, Jose F Perez-Zoghbi, Yi Zhang, Dingbang Xu, Amy Dee Wu, Dan E Berkowitz, Charles W Emala
Non-visual opsin receptors have recently been implicated in blue light mediated photorelaxation of smooth muscle in various organs. Since photorelaxation has not yet been demonstrated in airway smooth muscle (ASM) or in human tissues, we questioned whether functional opsin receptors are expressed in mouse and human ASM. Messenger RNA encoding the opsin 3 receptor was detected in both human and mouse airway smooth muscle. To demonstrate the functionality of the opsin receptors, we performed wire myography of ex vivo airway smooth muscle from mouse and human upper airways...
October 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Christian R Marks, Brian C Shonesy, Xiaohan Wang, Jason R Stephenson, Colleen Niswender, Roger J Colbran
Ca2+ calmodulin dependent protein kinase II (CaMKII) and metabotropic glutamate receptor 5 (mGlu5) are critical signaling molecules in synaptic plasticity and learning memory. Here, we demonstrate that mGlu5 is present in CaMKIIα complexes isolated from mouse forebrain. Further in vitro characterization showed that the membrane-proximal region of the C-terminal domain (CTD) of mGlu5a directly interacts with purified Thr286-autophosphorylated (activated) CaMKIIα. However, the binding of CaMKIIα to this CTD fragment is reduced by the addition of excess Ca2+/calmodulin or by additional CaMKIIα autophosphorylation at non-Thr286 sites...
October 3, 2018: Molecular Pharmacology
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