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Protein kinase G

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https://www.readbyqxmd.com/read/28102545/-rice-calcium-dependent-protein-kinase-oscpk17-targets-plasma-membrane-intrinsic-protein-and-sucrose-phosphate-synthase-and-is-required-for-a-proper-cold-stress-response
#1
M Cecília Almadanim, Bruno M Alexandre, Margarida T G Rosa, Helena Sapeta, António E Leitão, José C Ramalho, TuKiet T Lam, Sónia Negrão, Isabel A Abreu, M Margarida Oliveira
Calcium-dependent protein kinases (CDPKs) are involved in plant tolerance mechanisms to abiotic stresses. Although CDPKs are recognized as key messengers in signal transduction, the specific role of most members of this family remains unknown. Here we test the hypothesis that OsCPK17 plays a role in rice cold stress response by analyzing OsCPK17 knockout, silencing, and overexpressing rice lines under low temperature. Altered OsCPK17 gene expression compromises cold tolerance performance, without affecting the expression of key cold stress-inducible genes...
January 19, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28102363/smarca4-inactivating-mutations-increase-sensitivity-to-aurora-kinase-a-inhibitor-vx-680-in-non-small-cell-lung-cancers
#2
Vural Tagal, Shuguang Wei, Wei Zhang, Rolf A Brekken, Bruce A Posner, Michael Peyton, Luc Girard, TaeHyun Hwang, David A Wheeler, John D Minna, Michael A White, Adi F Gazdar, Michael G Roth
Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28102353/cofilin-regulates-nuclear-architecture-through-a-myosin-ii-dependent-mechanotransduction-module
#3
O'Neil Wiggan, Bryce Schroder, Diego Krapf, James R Bamburg, Jennifer G DeLuca
Structural features of the nucleus including shape, size and deformability impact its function affecting normal cellular processes such as cell differentiation and pathological conditions such as tumor cell migration. Despite the fact that abnormal nuclear morphology has long been a defining characteristic for diseases such as cancer relatively little is known about the mechanisms that control normal nuclear architecture. Mounting evidence suggests close coupling between F-actin cytoskeletal organization and nuclear morphology however, mechanisms regulating this coupling are lacking...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101188/mir-125a-3p-targetedly-regulates-git1-expression-to-inhibit-osteoblastic-proliferation-and-differentiation
#4
Xiao-Mei Tu, Yang-Lin Gu, Guo-Qin Ren
Osteoblasts are a prerequisite for osteogenesis and bone formation, and play a key role in metabolic balance, growth, development and wound repair. G protein-coupled receptor kinase interacting protein 1 (GIT1) and a series of miRNAs are known to have important effects in the growth and migration of osteoblasts, but little is known about micro RNAs (miRNAs) targeting GIT1. The present study found that miR-125a-3p has matching sites on GIT1. In the osteoblastic differentiation process of human bone marrow-derived mesenchymal stem cells (HMSCs), the expression of miR-125a-3p was suppressed compared with that in non-differentiating (HMSCs) while the expression of GIT1 showed a gradual and significant increase...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100897/x-indening-oral-liquid-improves-cardiac-function-of-rats-with-chronic-cardiac-failure-via-tgf-%C3%A3-1-smad3-and-p38-mapk-pathway
#5
Yunliang Wei, Changsheng Guo, Jingsheng Zhao, Jun Yang, Weiguo Yi, Hong Liu, Xinwei Lin, Zhengchen Zhang
OBJECTIVE: Xindening oral liquid (Xin) is a widely used traditional Chinese medicine for the treatment of chronic heart failure (CHF). However, the exact mechanisms related to its therapeutic effects against CHF remain unclear. In the present study, we investigate the effects of Xin on cardiac function in CHF rats and the possible mechanisms involved. METHODS: Transverse aortic constriction (TAC) was conducted to induce a CHF rat model in this study. Sixty male Wistar rats were randomly assigned to six groups 28 days after TAC: sham; CHF model; Xin at concentrations of 5 ml/kg, 10 mL/kg, and 20 mL/kg; and QiLi 0...
January 17, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28100636/centriole-splitting-caused-by-loss-of-the-centrosomal-linker-protein-c-nap1-reduces-centriolar-satellite-density-and-impedes-centrosome-amplification
#6
Anne-Marie Flanagan, Elena Stavenschi, Shivakumar Basavaraju, David Gaboriau, David A Hoey, Ciaran G Morrison
Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1 null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with re-expression of C-NAP1 rescuing both these phenotypes...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28100502/rack1-regulates-angiotensin-ii-induced-contractions-of-shr-preglomerular-vascular-smooth-muscle-cells
#7
Xiao Zhu, Edwin K Jackson
The preglomerular microcirculation of spontaneously hypertensive rats (SHR) is hypersensitive to angiotensin II, and studies show that this is likely due to enhanced convergent signaling between G-protein subunits αq (Gαq; released by angiotensin II) and G-protein subunits βγ (Gβγ; released by Gi-coupled receptors) to active phospholipase C (PLC). Here we investigated the molecular basis for the enhanced convergent signaling between Gβγ and Gαq in SHR preglomerular vascular smooth muscle cells (PGVSMCs)...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#8
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099503/3d-functional-corneal-stromal-tissue-equivalent-based-on-corneal-stromal-stem-cells-and-multi-layered-silk-film-architecture
#9
Chiara E Ghezzi, Benedetto Marelli, Fiorenzo G Omenetto, James L Funderburgh, David L Kaplan
The worldwide need for human cornea equivalents continues to grow. Few clinical options are limited to allogenic and synthetic material replacements. We hypothesized that tissue engineered human cornea systems based on mechanically robust, patterned, porous, thin, optically clear silk protein films, in combination with human corneal stromal stem cells (hCSSCs), would generate 3D functional corneal stroma tissue equivalents, in comparison to previously developed 2D approaches. Silk film contact guidance was used to control the alignment and distribution of hCSSCs on RGD-treated single porous silk films, which were then stacked in an orthogonally, multi-layered architecture and cultured for 9 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#10
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28098256/dopamine-promotes-nmda-receptor-hypofunction-in-the-retina-through-d1-receptor-mediated-csk-activation-src-inhibition-and-decrease-of-glun2b-phosphorylation
#11
Renato Socodato, Felipe N Santiago, Camila C Portugal, Ivan Domith, Thaísa G Encarnação, Erick C Loiola, Ana L M Ventura, Marcelo Cossenza, João B Relvas, Newton G Castro, Roberto Paes-de-Carvalho
Dopamine and glutamate are critical neurotransmitters involved in light-induced synaptic activity in the retina. In brain neurons, dopamine D1 receptors (D1Rs) and the cytosolic protein tyrosine kinase Src can, independently, modulate the behavior of NMDA-type glutamate receptors (NMDARs). Here we studied the interplay between D1Rs, Src and NMDARs in retinal neurons. We reveal that dopamine-mediated D1R stimulation provoked NMDAR hypofunction in retinal neurons by attenuating NMDA-gated currents, by preventing NMDA-elicited calcium mobilization and by decreasing the phosphorylation of NMDAR subunit GluN2B...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096179/dbf4-dependent-kinase-and-the-rtt107-scaffold-promote-mus81-mms4-resolvase-activation-during-mitosis
#12
Lissa N Princz, Philipp Wild, Julia Bittmann, F Javier Aguado, Miguel G Blanco, Joao Matos, Boris Pfander
DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner...
January 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28094871/divergence-of-camp-signaling-pathways-mediating-augmented-nucleotide-excision-repair-and-pigment-induction-in-melanocytes
#13
Erin M Wolf Horrell, Stuart G Jarrett, Katharine M Carter, John A D'Orazio
Loss-of-function melanocortin 1 receptor (MC1R) polymorphisms are common in UV-sensitive fair-skinned individuals and are associated with blunted cAMP second messenger signaling and higher lifetime risk of melanoma because of diminished ability of melanocytes to cope with UV damage. cAMP signaling positions melanocytes to resist UV injury by up-regulating synthesis of UV-blocking eumelanin pigment and by enhancing the repair of UV-induced DNA damage. cAMP enhances melanocyte nucleotide excision repair (NER), the genome maintenance pathway responsible for the removal of mutagenic UV photolesions, through cAMP-activated protein kinase (protein kinase A)-mediated phosphorylation of the ataxia telangiectasia mutated and Rad3 related (ATR) protein on the S435 residue...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#14
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28091904/effects-of-release-active-antibodies-to-cd4-receptor-on-the-level-of-lck-kinase-in-cultured-mononuclear-cells-from-human-peripheral-blood
#15
A G Emel'yanova, V V Grechenko, N V Petrova, I P Shilovskii, E A Gorbunov, S A Tarasov, M R Khaitov, S G Morozov, O I Epshtein
For evaluation of effects of release-active antibodies to CD4 on cultured lymphocytes from human peripheral blood, we measured intracellular content of lck-kinase cell-based ELISA. In cells treated with release-active antibodies to CD4, the content of intracellular lck-kinase significantly (p<0.01) decreased in comparison with the control (purified water processed in a similar way). Phytohemagglutinin had no effect on the concentration of lck-kinase in cells. The decrease in the content of CD4-associated lck protein suggests that the preparation enhanced intracellular coupling of lck-kinase with T-cell receptor and potentiated T-cell immune response...
January 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28090628/erk1-2-jnk-and-stat3-activation-and-correlation-with-tumor-differentiation-in-oral-scc
#16
I Gkouveris, N Nikitakis, D Avgoustidis, M Karanikou, G Rassidakis, A Sklavounou
Signal transducer and activator of transcription 3 (STAT3) and mitogen activated protein kinases (MAPKs), including ERK and JNK, have been implicated in oral squamous cell carcinoma (OSCC) development and progression. Our purpose was to evaluate the levels of activated STAT3, ERK1/2 and JNK by immunohistochemistry in OSCC and to investigate possible correlations of these molecules with each other as well as with the degree of tumor differentiation. Immunohistochemical assessment of the phosphorylated levels of STAT3(tyrosine/ serine), ERK1/2 and JNK was performed in 60 OSCC, including well, moderately and poorly differentiated tumors...
January 16, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28088959/-effect-of-exendin-4-on-lipid-deposition-in-skeletal-muscle-of-diet-induced-obese-mice-and-its-underlying-mechanism
#17
H Y Cao, F Xu, Z L Chen, B S Lin, X B Zheng, S H Yuan, H Liang, J P Weng
Objective: To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice. Methods: Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg(-1)·d(-1) exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group...
January 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28088894/clinical-significance-of-the-sympathetic-nervous-system-in-the-development-and-progression-of-pulmonary-arterial-hypertension
#18
Ru-Xia Liu, Qian Luo, Hui Qiao, Juan Yu, Qian-Long Zhang, Peng Wang, Yong-Gang Cao, Chang-Lin Jiang, Li-Hui Qu
Pulmonary arterial hypertension (PAH) is defined as a complex disease of clinically characterized by elevated pulmonary pressure eventually resulting in right heart failure and premature death. To date, PAH still remains a life-threatening disease. Published evidence suggests that patients with PAH present profound sympathetic nervous system abnormalities and sympathetic activity has been shown to be increased. The mechanism of PAH is still complex and poorly understood. Some data have showed that adrenoceptors are involved in the process of the pathology and have different functions in the progression of PAH followed by heart failure...
January 12, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28088389/nalfurafine-is-a-g-protein-biased-agonist-having-significantly-greater-bias-at-the-human-than-rodent-form-of-the-kappa-opioid-receptor
#19
Selena S Schattauer, Jamie R Kuhar, Allisa Song, Charles Chavkin
Nalfurafine is a moderately selective kappa opioid receptor (KOR) analgesic with low incidence of dysphoric side effects in clinical development for the treatment of uremic pruritis. The basis for its reduced dysphoric effect compared to other KOR agonists is not clear, but prior studies suggest that the aversive properties of KOR agonists require p38α MAPK activation through an arrestin-dependent mechanism. To determine whether nalfurafine is a functionally selective KOR agonist, we measured its potency to activate the G protein-dependent early phase of Extracellular Signal-Regulated Kinase (ERK1/2) phosphorylation and the arrestin-dependent late phase of p38 MAPK signaling...
January 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28087840/vibrio-cholerae-cholix-toxin-induced-hepg2-cell-death-is-enhanced-by-tumor-necrosis-factor-alpha-through-ros-and-intracellular-signal-regulated-kinases
#20
Kohei Ogura, Yasuhiro Terasaki, Tohru Miyoshi-Akiyama, Mika Terasaki, Joel Moss, Masatoshi Noda, Kinnosuke Yahiro
Cholix toxin (Cholix) from Vibrio cholerae is a potent virulence factor exhibiting ADP-ribosyltransferase activity on eukaryotic elongation factor 2 (eEF2) of host cells, resulting in inhibition of protein synthesis. Administration of Cholix or its homologue Pseudomonas exotoxin A (PEA) to mice causes lethal hepatocyte damage. In this study, we demonstrate cytotoxicity of Cholix on immortalized human hepatocytes in the presence of tumor necrosis factor α (TNF-α), which has been reported to play a fatal role in PEA administered to mice...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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