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Protein kinase C

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https://www.readbyqxmd.com/read/28431242/structural-and-functional-analysis-of-a-%C3%AE-2-adrenergic-receptor-complex-with-grk5
#1
Konstantin E Komolov, Yang Du, Nguyen Minh Duc, Robin M Betz, João P G L M Rodrigues, Ryan D Leib, Dhabaleswar Patra, Georgios Skiniotis, Christopher M Adams, Ron O Dror, Ka Young Chung, Brian K Kobilka, Jeffrey L Benovic
The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on arrestin-mediated signaling. While a structural understanding of GPCR/G-protein and GPCR/arrestin complexes has emerged in recent years, the molecular architecture of a GPCR/GRK complex remains poorly defined. We used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β2-adrenergic receptor (β2AR)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431022/cpp1-phosphatase-mediated-signaling-crosstalk-between-hog1-and-cek1-mitogen-activated-protein-kinases-is-involved-in-the-phenotypic-transition-in-candida-albicans
#2
Fu-Sheng Deng, Ching-Hsuan Lin
Cellular signaling pathways involved in cell growth and differentiation mediated by mitogen-activated protein kinase (MAPK) cascades have been well characterized in fungi. However, the mechanisms of signaling crosstalk between MAPKs to ensure signaling specificity are largely unknown. Previous work showed that activation of the Candida albicans Cek1 MAPK pathway resulted in opaque cell formation and filamentation, which mirrored the phenotypes to hog1Δ. Additionally, deleting the HOG1 gene stimulated Cek1p...
April 20, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28430576/ezrin-activation-by-lok-phosphorylation-involves-a-pip2-dependent-wedge-mechanism
#3
Thaher Pelaseyed, Cécile Sauvanet, Raghuvir Viswanatha, Joshua J Filter, Michael L Goldberg, Anthony Bretscher
How cells specify morphologically distinct plasma membrane domains is poorly understood. Prior work has shown that restriction of microvilli to the apical aspect of epithelial cells requires the localized activation of the membrane-F-actin linking protein ezrin. Using an in vitro system, we now define a multi-step process whereby the kinase LOK specifically phosphorylates ezrin to activate it. Binding of PIP2 to ezrin induces a conformational change permitting the insertion of the LOK C-terminal domain to wedge apart the membrane and F-actin-binding domains of ezrin...
April 21, 2017: ELife
https://www.readbyqxmd.com/read/28430399/targeting-conformational-activation-of-cdk2-kinase
#4
Morgan Pellerano, Sergey Tcherniuk, Corine Perals, Thi Nhu Ngoc Van, Elsa Garcin, Florence Mahuteau-Betzer, Marie-Paule Teulade-Fichou, May C Morris
Cyclin-dependent kinases constitute attractive pharmacological targets for cancer therapeutics, yet inhibitors in clinical trials target the ATP-binding pocket of the CDK and therefore suffer from limited selectivity and emergence of resistance. The more recent development of allosteric inhibitors targeting conformational plasticity of protein kinases offers promising perspectives for therapeutics. In particular tampering with T-loop dynamics of CDK2 kinase would provide a selective means of inhibiting this kinase, by preventing its conformational activation...
April 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28430185/phospholipase-c%C3%AE-1-regulates-p38-mapk-activity-and-skin-barrier-integrity
#5
Kaori Kanemaru, Yoshikazu Nakamura, Kengo Totoki, Takatsugu Fukuyama, Madoka Shoji, Hisae Kaneko, Kanako Shiratori, Atsuko Yoneda, Takafumi Inoue, Yoichiro Iwakura, Kenji Kabashima, Kiyoko Fukami
Keratinocytes undergo a unique type of programmed cell death known as cornification, which leads to the formation of the stratum corneum (SC), the main physical barrier of the epidermis. A defective epidermal barrier is a hallmark of the two most common inflammatory skin disorders, psoriasis, and atopic dermatitis. However, the detailed molecular mechanisms of skin barrier formation are not yet fully understood. Here, we showed that downregulation of phospholipase C (PLC) δ1, a Ca(2+)-mobilizing and phosphoinositide-metabolizing enzyme abundantly expressed in the epidermis, impairs the barrier functions of the SC...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28430130/timp1-promotes-cell-survival-by-activating-the-pdk1-signaling-pathway-in-melanoma
#6
Mariana Toricelli, Fabiana H M Melo, Aline Hunger, Daniela Zanatta, Bryan E Strauss, Miriam G Jasiulionis
High TIMP1 expression is associated with poor prognosis in melanoma, where it can bind to CD63 and β1 integrin, inducing PI3-kinase pathway and cell survival. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), generated under phosphatidylinositol-3-kinase (PI3K) activation, enables the recruitment and activation of protein kinase B (PKB/AKT) and phosphoinositide-dependent kinase 1 (PDK1) at the membrane, resulting in the phosphorylation of a host of other proteins. Using a melanoma progression model, we evaluated the impact of Timp1 and AKT silencing, as well as PI3K, PDK1, and protein kinase C (PKC) inhibitors on aggressiveness characteristics...
April 21, 2017: Cancers
https://www.readbyqxmd.com/read/28430012/zo-1-expression-is-suppressed-by-gm-csf-via-mir-96-erg-in-brain-microvascular-endothelial-cells
#7
Hu Zhang, Shuhong Zhang, Jilin Zhang, Dongxin Liu, Jiayi Wei, Wengang Fang, Weidong Zhao, Yuhua Chen, Deshu Shang
The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28429673/hydroxytyrosol-attenuates-lps-induced-acute-lung-injury-in-mice-by-regulating-autophagy-and-sirtuin-expression
#8
X Yang, T Jing, Y Li, Y He, B Wang, W Zhang, Y Xiao, W Wang, J Zhang, J Wei, R Lin
BACKGROUND: Recently, the effects of hydroxytyrosol on autophagy during acute lung injury (ALI) have drawn increasing attention. OBJECTIVE: We explored the underlying molecular mechanisms by which hydroxytyrosol exerts its anti-inflammatory effects in a murine model of ALI by up-regulating autophagy. METHODS: Male BALB/c mice, challenged with intranasal instillations of LPS, were treated with or without hydroxytyrosol (HT, 100 mg/kg, intragastrically) 1 h prior to LPS exposure...
April 21, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429504/induced-pluripotent-stem-cells-reduce-neutrophil-chemotaxis-via-activating-grk2-in-endotoxin-induced-acute-lung-injury
#9
Vincent Yi-Fong Su, Shih-Hwa Chiou, Chi-Shiuan Lin, Wei-Chih Chen, Wen-Kuang Yu, Yen-Wen Chen, Cheng-Yu Chen, Kuang-Yao Yang
BACKGROUND AND OBJECTIVE: We investigated the effect of induced pluripotent stem cells (iPSCs) in moderating neutrophil chemotaxis in endotoxin-induced acute lung injury (ALI). METHODS: Male C57BL/6 mice at 8-12 weeks of age were studied. Murine iPSCs were delivered through the tail veins of mice 4 h after intratracheal instillation of endotoxin. Lung histopathological findings, neutrophil counts in peripheral blood and bronchoalveolar lavage fluid (BALF), bone marrow (BM) cell distribution, expression of chemokine receptors and regulatory signalling pathways were analysed after 24 h...
April 21, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28429284/foxo1-attenuates-naf-induced-apoptosis-of-ls8-cells-through-the-jnk-and-mitochondrial-pathways
#10
Juedan Li, Lin Zhao, Xiaomeng Zhao, Peng Wang, Yan Liu, Jianping Ruan
Fluoride-induced ameloblast apoptosis is a key event in dental fluorosis development. Forkhead box o1 (Foxo1) is a transcription factor involved in cell apoptosis. The present study aims to investigate the effect of Foxo1 on ameloblast apoptosis induced by fluoride in vitro and to explore its possible mechanism. Ameloblast-like cells (LS8 cells) were exposed to various concentrations of NaF for up to 48 h. Foxo1 activation was modulated using lentiviral vectors, and cell apoptosis was measured by flow cytometry...
April 20, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28429187/curcumin-reverses-the-depressive-like-behavior-and-insulin-resistance-induced-by-chronic-mild-stress
#11
Ji-Duo Shen, Yu Wei, Yu-Jie Li, Jing-Yi Qiao, Yu-Cheng Li
Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity...
April 21, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28428969/targeted-lung-cancer-treatments-and-eye-metastasis
#12
REVIEW
Paul Zarogoulidis, Sofia Baka, Sofia Labaki, George Lazaridis, Georgia Trakada
Lung cancer remains the leading cause of death due to cancer. We do not have effective tools for the early detection of lung cancer, so patients are usually diagnosed at an advanced stage. However, novel therapies based on molecular pathways (such as those involving the epidermal growth factor receptor, anaplastic lymphoma kinase, serine/threonine-protein kinase B-Raf, proto-oncogene tyrosine-protein kinase ROS, c-Met proto-oncogene protein, and RET proto-oncogene protein) are now commonly used in the treatment of lung cancer...
2017: Medical Hypothesis, Discovery and Innovation in Ophthalmology
https://www.readbyqxmd.com/read/28428274/egfr-mediates-responses-to-small-molecule-drugs-targeting-oncogenic-fusion-kinases
#13
Aria Vaishnavi, Laura Schubert, Uwe Rix, Lindsay A Marek, Anh T Le, Stephen Keysar, Magdalena J Glogowska, Matthew A Smith, Severine L Kako, Natalia J Sumi, Kurtis D Davies, Kathryn E Ware, Marileila Varella-Garcia, Eric B Haura, Antonio Jimeno, Lynn E Heasley, Dara L Aisner, Robert C Doebele
Oncogenic kinase fusions of ALK, ROS1, RET and NTRK1 act as drivers in human lung and other cancers. Residual tumor burden following treatment of ALK or ROS1+ lung cancer patients with oncogene-targeted therapy ultimately enables the emergence of drug-resistant clones, limiting the long-term effectiveness of these therapies. To determine the signaling mechanisms underlying incomplete tumor cell killing in oncogene-addicted cancer cells, we investigated the role of EGFR signaling in drug-naive cancer cells harboring these oncogene fusions...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428258/deletion-of-inositol-requiring-enzyme-1%C3%AE-in-podocytes-disrupts-glomerular-capillary-integrity-and-autophagy
#14
Daniel Robert Kaufman, Joan Papillon, Louise Larose, Takao Iwawaki, Andrey V Cybulsky
Inositol-requiring enzyme-1α (IRE1α) is an endoplasmic reticulum (ER)-transmembrane endoribonuclease-kinase, which plays an essential function in extraembryonic tissues during normal development, and is activated during ER stress. To address the functional role of IRE1α in glomerular podocytes, we produced podocyte-specific IRE1α deletion mice. In male mice, deletion of IRE1α in podocytes resulted in albuminuria beginning at 5 months of age, and worsening with time. Electron microscopy revealed focal podocyte foot process effacement in 9-month old male IRE1α deletion mice, as well as microvillous transformation of podocyte plasma membranes...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428253/twitchin-kinase-inhibits-muscle-activity
#15
Yohei Matsunaga, Hyundoo Hwang, Barbara Franke, Rhys Williams, McKenna Penley, Hiroshi Qadota, Hong Yi, Levi T Morran, Hang Lu, Olga Mayans, Guy M Benian
Muscle sarcomeres contain giant polypeptides composed of multiple immunoglobulin and fibronectin domains and one or two protein kinase domains. Although binding partners for a number of this family's kinase domains have been identified, the catalytic necessity of these kinase domains remains unknown. In addition, various members of this kinase family are suspected pseudokinases with no, or little, activity. Here, we address catalytic necessity for the first time using the prototypic invertebrate representative twitchin (UNC-22) from C...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428249/crystal-structure-and-redox-properties-of-a-novel-cyanobacterial-heme-protein-with-a-his-cys-heme-axial-ligation-and-a-per-arnt-sim-pas-like-domain
#16
Taiki Motomura, Michihiro Suga, Rainer Hienerwadel, Akiko Nakagawa, Thanh-Lan Lai, Wolfgang Nitschke, Takahiro Kuma, Miwa Sugiura, Alain Boussac, Jain-Ren Shen
Photosystem II (PSII) catalyzes the light-induced water oxidation leading to the generation of dioxygen indispensable for sustaining aerobic life on Earth. The PSII reaction center is composed of D1 and D2 proteins encoded by the psbA and psbD genes, respectively. In cyanobacteria, different psbA genes are present in the genome. The thermophilic cyanobacterium Thermosynechococcus elongatus contains 3 psbA genes, psbA1, psbA2 and psbA3 and a new c-type heme protein, Tll0287, was found to be expressed in a strain expressing the psbA2 gene only, but the structure and function of Tll0287 are unknown...
April 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28428115/p300-and-c-ebp%C3%AE-regulated-ikk%C3%AE-expression-are-involved-in-thrombin-induced-il-8-cxcl8-expression-in-human-lung-epithelial-cells
#17
Zheng-Wei Huang, Gi-Shih Lien, Chien-Huang Lin, Chun-Ping Jiang, Bing-Chang Chen
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic lung inflammatory diseases. Thrombin and interleukin (IL)-8/C-X-C chemokine ligand 8 (CXCL8) play critical roles in lung inflammation. Our previous study showed that c-Src-dependent IκB kinase (IKK)/IκBα/nuclear factor (NF)-κB and mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/ribosomal S6 protein kinase (RSK)-dependent CAAT/enhancer-binding protein β (C/EBPβ) activation are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells...
April 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28428008/force-development-and-intracellular-ca-2-in-intact-cardiac-muscles-from-gravin-mutant-mice
#18
Zhitao Li, Sonal Singh, Santosh V Suryavanshi, Wengang Ding, Xiaoxu Shen, Cori S Wijaya, Wei Dong Gao, Bradley K McConnell
Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A (PKA), β2-adrenergic receptor (β2-AR), protein phosphatase 2B and protein kinase C. Gravin facilitates β2-AR-dependent signal transduction through PKA to modulate cardiac excitation-contraction coupling and its removal positively affects cardiac contraction. Trabeculae from the right ventricles of gravin mutant (gravin-t/t) mice were employed for force determination. Simultaneously, corresponding intracellular Ca(2+) transient ([Ca(2+)]i) were measured...
April 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28427942/inhibitory-effects-of-ethyl-pyruvate-on-platelet-aggregation-and-phosphatidylserine-exposure
#19
Wenjin Li, Xinyu Yang, Minyuan Peng, Can Li, Guangfu Mu, Fangping Chen
Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation and coagulation are closely interacted with platelet activation. However, it is unclear whether EP has anti-platelet effects. Therefore, we investigated the anti-platelet effect of EP in this study in vitro. We found that EP inhibited agonists induced platelets aggregation, ATP release and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L expression...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28427866/effect-of-amyloid-%C3%AE-25-35-in-hyperglycemic-and-hyperinsulinemic-rats-effects-on-phosphorylation-and-o-glcnacylation-of-tau-protein
#20
Liliana Lozano, Jorge Guevara, Tony Lefebvre, Ivan Ramos-Martinez, Daniel Limón, Alfonso Díaz, Eduarda Cerón, Edgar Zenteno
Aggregation of the amyloid beta (Aβ) peptide and hyperphosphorylation of tau protein, which are markers of Alzheimer's disease (AD), have been reported also in diabetes mellitus (DM). One regulator of tau phosphorylation is O-GlcNAcylation, whereas for hyperphosphorylation it could be GSK3beta, which is activated in hyperglycemic conditions. With this in mind, both O-GlcNAcylation and phosphorylation of tau protein were evaluated in the brain of rats with streptozotocin (STZ)-induced hyperglycemia and hyperinsulinemia and treated with the Aß25-35 peptide in the hippocampal region CA1...
April 6, 2017: Neuropeptides
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