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Protein Kinase

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https://www.readbyqxmd.com/read/28107777/the-dc1-domain-protein-vacuoleless-gametophytes-is-essential-for-female-and-male-gametophyte-development-in-arabidopsis
#1
Sebastián D'Ippólito, Leonardo Agustín Arias, Claudia Anahí Casalongué, Gabriela Carolina Pagnussat, Diego Fernando Fiol
In this work we identified VACUOLELESS GAMETOPHYTES (VLG) as a DC1 domain containing protein present in the endomembrane system essential for both female and male gametophyte development. VLG was originally annotated as a gene coding for an unknown function protein containing DC1 domains. DC1 domains are cysteine and histidine -rich zinc finger domains found exclusively in the plant Kingdom that have been named based on its similarity with the C1 domain present in protein kinase C (PKC). In Arabidopsis, both male and female gametophytes are characterized by the formation of a big vacuole early in development, which is absent in vlg mutant plants...
January 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28107751/molecular-modeling-study-of-cp-690550-derivatives-as-jak3-kinase-inhibitors-through-combined-3d-qsar-molecular-docking-and-dynamics-simulation-techniques
#2
Jing Li Wang, Li Ping Cheng, Tian Chi Wang, Wei Deng, Fan Hong Wu
To develop more potent JAK3 kinase inhibitors, a series of CP-690550 derivatives were investigated using combined molecular modeling techniques, such as 3D-QSAR, molecular docking and molecular dynamics (MD). The leave-one-out correlation (q(2)) and non-cross-validated correlation coefficient (r(2)) of the best CoMFA model are 0.715 and 0.992, respectively. The q(2) and r(2) values of the best CoMSIA model are 0.739 and 0.995, respectively. The steric, electrostatic, and hydrophobic fields played important roles in determining the inhibitory activity of CP-690550 derivatives...
January 4, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#3
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#4
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase has been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28107519/cudraflavone-c-induces-tumor-specific-apoptosis-in-colorectal-cancer-cells-through-inhibition-of-the-phosphoinositide-3-kinase-pi3k-akt-pathway
#5
Hsien-Chuen Soo, Felicia Fei-Lei Chung, Kuan-Hon Lim, Veronica Alicia Yap, Tracey D Bradshaw, Ling-Wei Hii, Si-Hoey Tan, Sze-Jia See, Yuen-Fen Tan, Chee-Onn Leong, Chun-Wai Mai
Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumor-selective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28107516/liver-amp-activated-protein-kinase-is-unnecessary-for-gluconeogenesis-but-protects-energy-state-during-nutrient-deprivation
#6
Clinton M Hasenour, D Emerson Ridley, Freyja D James, Curtis C Hughey, E Patrick Donahue, Benoit Viollet, Marc Foretz, Jamey D Young, David H Wasserman
AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes...
2017: PloS One
https://www.readbyqxmd.com/read/28107512/nonstructural-5a-protein-of-hepatitis-c-virus-interferes-with-toll-like-receptor-signaling-and-suppresses-the-interferon-response-in-mouse-liver
#7
Takeya Tsutsumi, Kazuya Okushin, Kenichiro Enooku, Hidetaka Fujinaga, Kyoji Moriya, Hiroshi Yotsuyanagi, Hideki Aizaki, Tetsuro Suzuki, Yoshiharu Matsuura, Kazuhiko Koike
The hepatitis C virus nonstructural protein NS5A is involved in resistance to the host immune response, as well as the viral lifecycle such as replication and maturation. Here, we established transgenic mice expressing NS5A protein in the liver and examined innate immune responses against lipopolysaccharide (LPS) in vivo. Intrahepatic gene expression levels of cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ were significantly suppressed after LPS injection in the transgenic mouse liver...
2017: PloS One
https://www.readbyqxmd.com/read/28107427/serine-phosphorylation-of-slp76-is-dispensable-for-t-cell-development-but-modulates-helper-t-cell-function
#8
Victor H Navas, Céline Cuche, Andres Alcover, Vincenzo Di Bartolo
The adapter protein SLP76 is a key orchestrator of T cell receptor (TCR) signal transduction. We previously identified a negative feedback loop that modulates T cell activation, involving phosphorylation of Ser376 of SLP76 by the hematopoietic progenitor kinase 1 (HPK1). However, the physiological relevance of this regulatory mechanism was still unknown. To address this question, we generated a SLP76-S376A-expressing knock-in mouse strain and investigated the effects of Ser376 mutation on T cell development and function...
2017: PloS One
https://www.readbyqxmd.com/read/28107387/neuronal-cell-death-and-degeneration-through-increased-nitroxidative-stress-and-tau-phosphorylation-in-hiv-1-transgenic-rats
#9
Young-Eun Cho, Myoung-Hwa Lee, Byoung-Joon Song
The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28107384/an-approach-to-elucidate-nbs1-function-in-dna-repair-using-frequent-nonsynonymous-polymorphism-in-wild-medaka-oryzias-latipes-populations
#10
Kento Igarashi, Junya Kobayashi, Takafumi Katsumura, Yusuke Urushihara, Kyohei Hida, Tomomi Watanabe-Asaka, Hiroki Oota, Shoji Oda, Hiroshi Mitani
Nbs1 is one of the genes responsible for Nijmegen breakage syndrome, which is marked with high radiosensitivity. In human NBS1 (hNBS1), Q185E polymorphism is known as the factor to cancer risks, although its DSB repair defect has not been addressed. Here we investigated the genetic variations in medaka (Oryzias latipes) wild populations, and found 40 nonsynonymous single nucleotide polymorphisms (SNPs) in medaka nbs1 (olnbs1) gene within 5 inbred strains. A mutation to histidine in Q170 residue in olNbs1, which corresponds to Q185 residue of hNBS1, was widely distributed in the closed colonies derived from the eastern Korean population of medaka...
2017: PloS One
https://www.readbyqxmd.com/read/28107201/homeodomain-interacting-protein-kinase-2-hipk2-a-promising-target-for-anti-cancer-therapies
#11
Yuanyuan Feng, Lihong Zhou, Xiaoting Sun, Qi Li
The HIPK2 (serine/threonine homeodomain-interacting protein kinase 2) is a "caretaker" gene, its inactivation increases tumorigenicity while its activation inhibits tumor growth. This report reviews the anti-tumorigenic mechanisms of HIPK2, which include promotion of apoptosis, inhibition of angiogenesis in hypoxia, prevention of tumor invasion/metastasis and attenuation of multidrug resistance in cancer. Additionally, we summarize conditions or factors that may increase HIPK2 activity.
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106845/post-translational-modifications-of-the-tak1-tab-complex
#12
REVIEW
Yusuke Hirata, Miki Takahashi, Tohru Morishita, Takuya Noguchi, Atsushi Matsuzawa
Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that is activated by growth factors and cytokines such as TGF-β, IL-1β, and TNF-α, and mediates a wide range of biological processes through activation of the nuclear factor-κB (NF-κB) and the mitogen-activated protein (MAP) kinase signaling pathways. It is well established that activation status of TAK1 is tightly regulated by forming a complex with its binding partners, TAK1-binding proteins (TAB1, TAB2, and TAB3)...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106831/ablation-of-protein-kinase-ck2%C3%AE-in-skeletal-muscle-fibers-interferes-with-their-oxidative-capacity
#13
Nane Eiber, Luca Simeone, Said Hashemolhosseini
The tetrameric protein kinase CK2 was identified playing a role at neuromuscular junctions by studying CK2β-deficient muscle fibers in mice, and in cultured immortalized C2C12 muscle cells after individual knockdown of CK2α and CK2β subunits. In muscle cells, CK2 activity appeared to be at least required for regular aggregation of nicotinic acetylcholine receptors, which serves as a hallmark for the presence of a postsynaptic apparatus. Here, we set out to determine whether any other feature accompanies CK2β-deficient muscle fibers...
January 19, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28106827/neuroprotective-strategy-in-retinal-degeneration-suppressing-er-stress-induced-cell-death-via-inhibition-of-the-mtor-signal
#14
REVIEW
Bin Fan, Ying-Jian Sun, Shu-Yan Liu, Lin Che, Guang-Yu Li
The retina is a specialized sensory organ, which is essential for light detection and visual formation in the human eye. Inherited retinal degenerations are a heterogeneous group of eye diseases that can eventually cause permanent vision loss. UPR (unfolded protein response) and ER (endoplasmic reticulum) stress plays an important role in the pathological mechanism of retinal degenerative diseases. mTOR (the mammalian target of rapamycin) kinase, as a signaling hub, controls many cellular processes, covering protein synthesis, RNA translation, ER stress, and apoptosis...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106783/extract-of-polygala-tenuifolia-alleviates-stress-exacerbated-atopy-like-skin-dermatitis-through-the-modulation-of-protein-kinase-a-and-p38-mitogen-activated-protein-kinase-signaling-pathway
#15
Bongjun Sur, Bombi Lee, Ye Seul Yoon, Pooreum Lim, Riwon Hong, Mijung Yeom, Hyang Sook Lee, Hijoon Park, Insop Shim, Hyejung Lee, Young Pyo Jang, Dae-Hyun Hahm
Atopic dermatitis (AD) and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value of Polygala tenuifolia Willd. (PTW) for treating immobilization (IMO) stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA) was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106780/integrins-and-cell-metabolism-an-intimate-relationship-impacting-cancer
#16
REVIEW
Rehman Ata, Costin N Antonescu
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106738/6-paradol-and-6-shogaol-the-pungent-compounds-of-ginger-promote-glucose-utilization-in-adipocytes-and-myotubes-and-6-paradol-reduces-blood-glucose-in-high-fat-diet-fed-mice
#17
Chien-Kei Wei, Yi-Hong Tsai, Michal Korinek, Pei-Hsuan Hung, Mohamed El-Shazly, Yuan-Bin Cheng, Yang-Chang Wu, Tusty-Jiuan Hsieh, Fang-Rong Chang
The anti-diabetic activity of ginger powder (Zingiber officinale) has been recently promoted, with the recommendation to be included as one of the dietary supplements for diabetic patients. However, previous studies presented different results, which may be caused by degradation and metabolic changes of ginger components, gingerols, shogaols and paradols. Therefore, we prepared 10 ginger active components, namely 6-, 8-, 10-paradols, 6-, 8-, 10-shogaols, 6-, 8-, 10-gingerols and zingerone, and evaluated their anti-hyperglycemic activity...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106616/lymphocyte-phospho-ser-9-gsk-3%C3%AE-total-gsk-3%C3%AE-protein-levels-ratio-is-not-affected-by-chronic-lithium-or-valproate-treatment-in-euthymic-patients-with-bipolar-disorder
#18
Abed N Azab, Ella Vainer, Galila Agam, Yuly Bersudsky
BACKGROUND: Glycogen synthase kinase-3 (GSK-3) inhibition by lithium has been well established in vitro, but proof that this biochemical effect mediates lithium's beneficial action in patients with bipolar disorder is lacking. We studied whether lymphocyte GSK-3β activity measured indirectly in lithium- or valproate (VPA)-treated euthymic patients with bipolar disorder is different from controls. METHODS: Lymphocyte total and Ser-9-phospho-GSK-3β (inactive) levels were measured by Western blotting...
January 19, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28106280/erk1-directly-interacts-with-jnk1-leading-to-regulation-of-jnk1-c-jun-activity-and-cell-transformation
#19
Bong Seok Kang, Yoon Jin Hwang, Zigang Dong
ERK1 and ERK2 share a great deal of homology and have been presumed to have similar functions. Available antibodies recognize both isoforms making the elucidation of functional differences challenging. Mitogen-activated protein (MAP) kinase networks are commonly depicted in the literature as linear and sequential phosphorylation cascades; however, the activation of these pathways is not mutually exclusive. Little doubt exists that MAP kinases engage in crosstalk, but the extent or the direct effect of these "conversations" is unclear...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106155/secreted-mir-27a-induced-by-cyclic-stretch-modulates-the-proliferation-of-endothelial-cells-in-hypertension-via-grk6
#20
Lu Wang, Han Bao, Kai-Xuan Wang, Ping Zhang, Qing-Ping Yao, Xiao-Hu Chen, Kai Huang, Ying-Xin Qi, Zong-Lai Jiang
Abnormal proliferation of endothelial cells (ECs) is important in vascular remodeling during hypertension, but the mechanisms are still unclear. In hypertensive rats caused by abdominal aortic coarctation, the expression of G-protein-coupled receptor kinase 6 (GRK6) in ECs at common carotid artery was repressed in vivo, and EC proliferation was increased. 15% cyclic stretch in vitro, which mimics the pathologically increased stretch in hypertension, repressed EC GRK6 expression via paracrine control by vascular smooth muscle cells (VSMCs)...
January 20, 2017: Scientific Reports
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