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Protein kinase G

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https://www.readbyqxmd.com/read/28334166/grk5-regulates-social-behavior-via-suppression-of-mtorc1-signaling-in-medial-prefrontal-cortex
#1
Bing Niu, Peipei Liu, Minjie Shen, Cao Liu, Li Wang, Feifei Wang, Lan Ma
Impairments in social behaviors are features of a number of psychiatric diseases associated with subtle alterations in the medial prefrontal cortex (mPFC) circuitry. G protein-coupled receptor kinase (GRK) 5 is widely expressing in the cortex, however, its role in regulation of the mPFC activity and the development of social behaviors and psychiatric disorders is unclear. Here, we found that GRK5 dificiency in mice caused social behavior impairments. Further morphological, electrophysiological, and biochemical analyses showed abnormal postsynaptic ultrastructure, impaired excitatory synaptic transmission, the increased association of raptor with mTOR, and overactivated mTORC1-S6K signaling in the mPFC of Grk5-/- mice...
February 27, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28333553/cyclooxygenase-2-induction-by-amino-acid-deprivation-requires-p38-mitogen-activated-protein-kinase-in-human-glioma-cells
#2
Zhiwen Li, Chi-Ming Chang, Lanfang Wang, Ping Zhang, Hui-Kuo G Shu
Glioblastomas (GBMs) are malignant brain tumors that can outstrip nutrient supplies due to rapid growth. Cyclooxygenase-2 (COX-2) has been linked to GBMs and may contribute to their aggressive phenotypes. Amino acid starvation results in COX-2 mRNA and protein induction in multiple human glioma cell lines in a process requiring p38 mitogen-activated protein kinase (p38-MAPK) and the Sp1 transcription factor. Increased vascular endothelial growth factor expression results from starvation-dependent COX-2 induction...
March 23, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28332085/low-level-arsenic-causes-chronic-inflammation-and-suppresses-expression-of-phagocytic-receptors
#3
Priyanka Prasad, Dona Sinha
The impact of chronic low-level groundwater arsenic (As) exposure [in the range above the WHO-recommended limit of 10 g/L but ≤50 μg/L (permissible limit of As for many Asian countries)] was investigated for cross talk of inflammatory changes and expression of phagocytic receptors of exposed rural women (N, 45) from districts of 24 Parganas (south) and in matched control groups (N, 43) [As ≤10 μg/L] from the same district. Systemic inflammation was evident from the upregulated levels of pro-inflammatory mediators like tumor necrosis factor-α (TNF-α); interleukins (ILs) like IL-6, IL-8, and IL-12; and C-reactive protein (CRP) in the sera and upregulated expression of protein kinase B phosphorylated at ser473 (pAKTser473)/nuclear factor-κB (NF-κB)/TNF-α axis in the leukocytes of exposed women with respect to control...
March 22, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28331449/cyclin-d1-in-the-liver-role-of-noncanonical-signaling-in-liver-steatosis-and-hormone-regulation
#4
Kelley G Núñez, Janet Gonzalez-Rosario, Paul T Thevenot, Ari J Cohen
BACKGROUND: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. METHODS: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28331048/g-protein-coupled-receptor-kinase-3-and-protein-kinase-c-phosphorylate-the-distal-c-terminal-tail-of-the-chemokine-receptor-cxcr4-and-mediate-recruitment-of-beta-arrestin
#5
Jiansong Luo, John M Busillo, Ralf Stumm, Jeffrey L Benovic
Phosphorylation of G protein-coupled receptors (GPCRs) is a key event for cell signaling and regulation of receptor function. Previously, using tandem mass spectrometry, we identified two phosphorylation sites at the distal C-terminal tail of the chemokine receptor CXCR4, but were unable to determine which specific residues were phosphorylated. Here, we demonstrate that serines 346 and/or 347 (Ser-346/7) of CXCR4 are phosphorylated upon stimulation with the agonist CXCL12 as well as a CXCR4 pepducin, ATI-2341...
March 22, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28330559/dge-seq-analysis-of-mur3-related-arabidopsis-mutants-provides-insight-into-how-dysfunctional-xyloglucan-affects-cell-elongation
#6
Zongchang Xu, Meng Wang, Dachuan Shi, Gongke Zhou, Tiantian Niu, Michael G Hahn, Malcolm A O'Neill, Yingzhen Kong
Our previous study of the Arabidopsis mur3-3 mutant and mutant plants in which the mur3-3 phenotypes are suppressed (xxt2mur3-3, xxt5mur3-3, xxt1xxt2mur3-3 and 35Spro:XLT2:mur3-3) showed that hypocotyl cell elongation is decreased in plants that synthesize galactose-deficient xyloglucan. To obtain genome-wide insight into the transcriptome changes and regulatory networks that may be involved in this decreased elongation, we performed digital gene expression analyses of the etiolated hypocotyls of wild type (WT), mur3-3 and the four suppressor lines...
May 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28329914/ginsenoside-rg3-restores-hepatitis-c-virus-induced-aberrant-mitochondrial-dynamics-and-inhibits-virus-propagation
#7
Seong-Jun Kim, Jae Young Jang, Eun-Jung Kim, Eun Kyung Cho, Dae Gyun Ahn, Chonsaeng Kim, Han Seul Park, Soung Won Jeong, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Hong Soo Kim, Boo Sung Kim, Ji-Hyung Lee, Aleem Siddiqui
Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their treatment of patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine and other conditions, which may be linked to mitochondrial dysfunction. Here we show that clinically prescribed DAAs, including Sofosbuvir, affect mitochondrial dynamics...
March 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28329830/secondhand-smoke-prevalent-polycyclic-aromatic-hydrocarbon-binary-mixture-induced-specific-mitogenic-and-pro-inflammatory-cell-signaling-events-in-lung-epithelial-cells
#8
Ross S Osgood, Brad L Upham, Pierre R Bushel, Kalpana Velmurugan, Ka-Na Xiong, Alison K Bauer
Low molecular weight polycyclic aromatic hydrocarbons (LMW PAHs; < 206.3 g/mol) are prevalent and ubiquitous environmental contaminants, presenting a human health concern, and have not been as thoroughly studied as the high MW PAHs. LMW PAHs exert their pulmonary effects, in part, through P38-dependent and -independent mechanisms involving cell-cell communication and the production of pro-inflammatory mediators known to contribute to lung disease. Specifically, we determined the effects of two representative LMW PAHs, 1-methylanthracene (1-MeA) and fluoranthene (Flthn), individually and as a binary PAH mixture on the dysregulation of gap junctional intercellular communication (GJIC) and connexin 43 (Cx43), activation of mitogen activated protein kinases (MAPK), and induction of inflammatory mediators in a mouse non-tumorigenic alveolar type II cell line (C10)...
January 30, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28328745/gpcr-signaling-via-%C3%AE-arrestin-dependent-mechanisms
#9
Pierre-Yves Jean-Charles, Suneet Kaur, Sudha K Shenoy
β-arrestin1 (or arrestin2) and β-arrestin2 (or arrestin3) are ubiquitously expressed cytosolic adaptor proteins that were originally discovered for their inhibitory role in G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins. However, further biochemical characterization revealed that β-arrestins do not just 'block' the activated GPCRs, but trigger endocytosis and kinase activation leading to specific signaling pathways that can be localized on endosomes. The signaling pathways initiated by β-arrestins were also found to be independent of G protein activation by GPCRs...
March 17, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28328744/non-canonical-roles-of-grks-in-cardiovascular-signaling
#10
Sarah M Schumacher, Walter J Koch
G protein-coupled receptor kinases (GRKs) are classically known for their role in regulating the activity of the largest known class of membrane receptors, which influence diverse biological processes in every cell type in the human body. As researchers have tried to uncover how this family of kinases, containing only 7 members, achieves selective and coordinated control of receptors, they have uncovered a growing number of non-canonical activities for these kinases. These activities include phosphorylation of non-receptor targets and kinase-independent molecular interactions...
March 17, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28325821/phosphorylation-of-the-exocyst-protein-exo84-by-tbk1-promotes-insulin-stimulated-glut4-trafficking
#11
Maeran Uhm, Merlijn Bazuine, Peng Zhao, Shian-Huey Chiang, Tingting Xiong, Sheelarani Karunanithi, Louise Chang, Alan R Saltiel
Insulin stimulates glucose uptake through the translocation of the glucose transporter GLUT4 to the plasma membrane. The exocyst complex tethers GLUT4-containing vesicles to the plasma membrane, a process that requires the binding of the G protein (heterotrimeric guanine nucleotide-binding protein) RalA to the exocyst complex. We report that upon activation of RalA, the protein kinase TBK1 phosphorylated the exocyst subunit Exo84. Knockdown of TBK1 blocked insulin-stimulated glucose uptake and GLUT4 translocation; knockout of TBK1 in adipocytes blocked insulin-stimulated glucose uptake; and ectopic overexpression of a kinase-inactive mutant of TBK1 reduced insulin-stimulated glucose uptake in 3T3-L1 adipocytes...
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325781/hete-signals-through-g-protein-coupled-receptor-gpr75-gq-to-affect-vascular-function-and-trigger-hypertension
#12
Victor Garcia, Ankit Gilani, Brian Shkolnik, Varunkumar Pandey, Frank F Zhang, Rambabu Dakarapu, Shyam K Gandham, N R Reddy, Joan P Graves, Artiom Gruzdev, Darryl C Zeldin, Jorge H Capdevila, John R Falck, Michal L Schwartzman
Rationale: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 (CYP) eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction and vascular diseases. Objective: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists...
March 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28325216/an-update-on-src-family-of-nonreceptor-tyrosine-kinases-biology
#13
J Espada, J Martín-Pérez
The members of the Src family of nonreceptor tyrosine kinases (SFKs) are implicated in multiple signaling processes that regulate key cellular functions, including proliferation, migration, differentiation, and survival. SFKs are activated by a large number of receptors for growth factors, cytokines, steroid hormones, G protein-coupled receptors, and also by adhesion proteins and other signaling partners. Through their common modular kinase an adapter protein domains, SFKs critically contribute to diversify different signal inputs, weaving a complex and dynamic network of cellular responses...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28324061/progesterone-protects-against-bpa-induced-arrhythmias-in-female-rat-cardiac-myocytes-via-rapid-signaling
#14
Jianyong Ma, Kui Hong, Hong-Sheng Wang
Bisphenol A (BPA) is an estrogenic endocrine disrupting chemical (EDC) that has a range of potential adverse health effects. Previously we showed that acute exposure to BPA promoted arrhythmias in female rat hearts through estrogen receptor rapid signaling. Progesterone (P4) and estrogen have antagonistic or complementary actions in a number of tissues and systems. In the current study, we examined the influence, and possible protective effect, of P4 on the rapid cardiac actions of BPA in female rat cardiac myocytes...
January 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324005/insulin-inhibits-nrf2-gene-expression-via-heterogeneous-nuclear-ribonucleoprotein-f-k-in-diabetic-mice
#15
Anindya Ghosh, Shaaban Abdo, Shuiling Zhao, Chin-Han Wu, Yixuan Shi, Chao-Sheng Lo, Isabelle Chenier, Thierry Alquier, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
Oxidative stress induces endogenous antioxidants via nuclear factor erythroid 2-related factor 2 (Nrf2), potentially preventing tissue injury. We investigated whether insulin affects renal Nrf2 expression in type 1 diabetes (T1D) and studied its underlying mechanism. Insulin normalized hyperglycemia, hypertension, oxidative stress and renal injury, inhibited renal Nrf2 and angiotensinogen (Agt) gene expression and up-regulated heterogeneous nuclear ribonucleoprotein F (hnRNP F) and hnRNP K expression in Akita mice with T1D...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323887/involvement-of-small-g-protein-rhob-in-the-regulation-of-proliferation-adhesion-and-migration-by-dexamethasone-in-osteoblastic-cells
#16
Fei Diao, Kangyao Chen, Yan Wang, Yidong Li, Weidong Xu, Jian Lu, Yu-Xia Chen
Long-term exposure to therapeutic doses of glucocorticoids (GCs) results in bone remodeling, which frequently causes osteoporosis and fracture healing retardation because of the abnormality of osteoblastic proliferation and differentiation. The mechanisms of GCs' effect on osteoblasts are largely unknown. In this present study, we found that dexamethasone (Dex) could induce the expression of the small G protein, RhoB, in mRNA and protein levels in the osteoblast-derived osteosarcoma cell lines MG-63. The up-regulation of RhoB mRNA by Dex mainly occurs at posttranscriptional level by increasing its mRNA stability through PI-3K/Akt and p38 mitogen-activated protein kinase signaling pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28323621/smoc-can-act-as-both-an-antagonist-and-an-expander-of-bmp-signaling
#17
J Terrig Thomas, D Eric Dollins, Kristin R Andrykovich, Tehyen Chu, Brian G Stultz, Deborah A Hursh, Malcolm Moos
The matricellular protein SMOC (Secreted Modular Calcium binding protein) is conserved phylogenetically from vertebrates to arthropods. We showed previously that SMOC inhibits bone morphogenetic protein (BMP) signaling downstream of its receptor via activation of mitogen-activated protein kinase (MAPK) signaling. In contrast, the most prominent effect of the Drosophila orthologue, pentagone (pent), is expanding the range of BMP signaling during wing patterning. Using SMOC deletion constructs we found that SMOC-∆EC, lacking the extracellular calcium binding (EC) domain, inhibited BMP2 signaling, whereas SMOC-EC (EC domain only) enhanced BMP2 signaling...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28323425/structure-based-design-of-highly-selective-and-potent-g-protein-coupled-receptor-kinase-2-inhibitors-based-on-paroxetine
#18
Helen V Waldschmidt, Kristoff T Homan, Marilyn C Cato, Osvaldo Cruz-Rodríguez, Alessandro Cannavo, Michael W Wilson, Jianliang Song, Joseph Y Cheung, Walter J Koch, John J G Tesmer, Scott D Larsen
In heart failure, the β-adrenergic receptors (βARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing heart making them desirable therapeutic targets. The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor. Utilizing a structure based drug design approach we modified paroxetine to generate a small compound library. Included in this series is a highly potent and selective GRK2 inhibitor, 14as, with an IC50 of 30 nM against GRK2 and greater than 230-fold selectivity over other GRKs and kinases...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28322746/truncation-of-cxcl12-by-cd26-reduces-its-cxc-chemokine-receptor-4-and-atypical-chemokine-receptor-3-dependent-activity-on-endothelial-cells-and-lymphocytes
#19
Rik Janssens, Anneleen Mortier, Daiane Boff, Pieter Ruytinx, Mieke Gouwy, Bo Vantilt, Olav Larsen, Viktorija Daugvilaite, Mette M Rosenkilde, Marc Parmentier, Sam Noppen, Sandra Liekens, Jo Van Damme, Sofie Struyf, Mauro M Teixeira, Flávio A Amaral, Paul Proost
The chemokine CXCL12 or stromal cell-derived factor 1/SDF-1 attracts hematopoietic progenitor cells and mature leukocytes through the G protein-coupled CXC chemokine receptor 4 (CXCR4). In addition, it interacts with atypical chemokine receptor 3 (ACKR3 or CXCR7) and glycosaminoglycans. CXCL12 activity is regulated through posttranslational cleavage by CD26/dipeptidyl peptidase 4 that removes two N-terminal amino acids. CD26-truncated CXCL12 does not induce calcium signaling or chemotaxis of mononuclear cells...
March 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28320779/the-g2385r-risk-factor-for-parkinson-s-disease-enhances-chip-dependent-intracellular-degradation-of-lrrk2
#20
Iakov N Rudenko, Alice Kaganovich, Rebekah G Langston, Aleksandra Beilina, Kelechi Ndukwe, Ravindran Kumaran, Allissa A Dillman, Ruth Chia, Mark R Cookson
Autosomal dominant mutations in leucine-rich repeat kinase 2 ( LRRK2 ) are associated with Parkinson's disease (PD). Most pathogenic LRRK2 mutations result in amino-acid substitutions in the central ROC-COR-Kinase triple domain and affect enzymatic functions of the protein. However, there are several variants in LRRK2 , including the risk factor G2385R, that impact PD pathogenesis by unknown mechanisms. Previously, we have shown that G2385R LRRK2 has decreased kinase activity in vitro and altered affinity to LRRK2 interactors...
March 20, 2017: Biochemical Journal
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