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PAS kinase

E Matyja, W Grajkowska, K Stępień, E Naganska
Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection...
2016: Folia Neuropathologica
Chintan K Kikani, Xiaoying Wu, Litty Paul, Hana Sabic, Zuolian Shen, Arvind Shakya, Alexandra Keefe, Claudio Villanueva, Gabrielle Kardon, Barbara Graves, Dean Tantin, Jared Rutter
PAS domain containing protein kinase (Pask) is an evolutionarily conserved protein kinase implicated in energy homeostasis and metabolic regulation across eukaryotic species. We now describe an unexpected role of Pask in promoting the differentiation of myogenic progenitor cells, embryonic stem cells and adipogenic progenitor cells. This function of Pask is dependent upon its ability to phosphorylate Wdr5, a member of several protein complexes including those that catalyze histone H3 Lysine 4 trimethylation (H3K4me3) during transcriptional activation...
2016: ELife
Ioannis Panagopoulos, Ludmila Gorunova, Trond Viset, Sverre Heim
We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21)[8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA‑sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in‑frame TBCK‑P4HA2 and the reciprocal but out‑of‑frame P4HA2‑TBCK fusion transcripts. The putative TBCK‑P4HA2 protein would contain the kinase, the rhodanese‑like domain, and the Tre‑2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4‑hydroxylase...
September 15, 2016: Oncology Reports
Yohei Ohashi, Nicolas Soler, Miguel García Ortegón, Lufei Zhang, Marie L Kirsten, Olga Perisic, Glenn R Masson, John E Burke, Arjen J Jakobi, Apostolos A Apostolakis, Christopher M Johnson, Maki Ohashi, Nicholas T Ktistakis, Carsten Sachse, Roger L Williams
The phosphatidylinositol 3-kinase Vps34 is part of several protein complexes. The structural organization of heterotetrameric complexes is starting to emerge, but little is known about organization of additional accessory subunits that interact with these assemblies. Combining hydrogen-deuterium exchange mass spectrometry (HDX-MS), X-ray crystallography and electron microscopy (EM), we have characterized Atg38 and its human ortholog NRBF2, accessory components of complex I consisting of Vps15-Vps34-Vps30/Atg6-Atg14 (yeast) and PIK3R4/VPS15-PIK3C3/VPS34-BECN1/Beclin 1-ATG14 (human)...
September 14, 2016: Autophagy
Joanna Kaminska, Weronika Rzepnikowska, Anna Polak, Krzysztof Flis, Piotr Soczewka, Katarzyna Bala, Marzena Sienko, Marcin Grynberg, Pawel Kaliszewski, Agnieszka Urbanek, Kathryn Ayscough, Teresa Zoladek
Human Nedd4 ubiquitin ligase, or its variants, inhibit yeast cell growth by disturbing the actin cytoskeleton organization and dynamics, and lead to an increase in levels of ubiquitinated proteins. In a screen for multicopy suppressors which rescue growth of yeast cells producing Nedd4 ligase with an inactive WW4 domain (Nedd4w4), we identified a fragment of ATG2 gene encoding part of the Atg2 core autophagy protein. Expression of the Atg2-C1 fragment (aa 1074-1447) improved growth, actin cytoskeleton organization, but did not significantly change the levels of ubiquitinated proteins in these cells...
October 2016: International Journal of Biochemistry & Cell Biology
Tilman Schirmer
Cellular levels of the second messenger cyclic di-guanosine monophosphate (c-di-GMP) are determined by the antagonistic activities of diguanylate cyclases and specific phosphodiesterases. In a given bacterial organism, there are often multiple variants of the two enzymes, which are tightly regulated by a variety of external and internal cues due to the presence of specialized sensory or regulatory domains. Dependent on the second messenger level, specific c-di-GMP receptors then control fundamental cellular processes, such as bacterial life style, biofilm formation, and cell cycle control...
September 25, 2016: Journal of Molecular Biology
Yuefeng Cai, Luqing Pan, Jingjing Miao, Tong Liu
The aryl hydrocarbon receptor (AhR) belongs to the basic-helix-loop helix (bHLH) Per-Arnt-Sim (PAS) family of transcription factors. AhR has been known primarily for its role in the regulation of several drug and xenobiotic metabolizing enzymes, as well as the mediation of the toxicity of certain xenobiotics, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Although the AhR is well-studied as a mediator of the toxicity of certain xenobiotics in marine bivalves, the normal physiological function remains unknown...
November 2016: Ecotoxicology and Environmental Safety
Soshichiro Nagano, Patrick Scheerer, Kristina Zubow, Norbert Michael, Katsuhiko Inomata, Tilman Lamparter, Norbert Krauß
Agp1 is a canonical biliverdin-binding bacteriophytochrome from the soil bacterium Agrobacterium fabrum that acts as a light-regulated histidine kinase. Crystal structures of the photosensory core modules (PCMs) of homologous phytochromes have provided a consistent picture of the structural changes that these proteins undergo during photoconversion between the parent red light-absorbing state (Pr) and the far-red light-absorbing state (Pfr). These changes include secondary structure rearrangements in the so-called tongue of the phytochrome-specific (PHY) domain and structural rearrangements within the long α-helix that connects the cGMP-specific phosphodiesterase, adenylyl cyclase, and FhlA (GAF) and the PHY domains...
September 23, 2016: Journal of Biological Chemistry
Truc Kim, Jongkeun Choi, Sangho Lee, Kwon Joo Yeo, Hae-Kap Cheong, Kyeong Kyu Kim
Bacterial two-component signal transduction systems are used to adapt to fluctuations in the environment. YycG, a key two-component histidine kinase in Staphylococcus aureus, plays an essential role in cell viability and regulates cell wall metabolism, biofilm formation, virulence, and antibiotic resistance. For these reasons, YycG is considered a compelling target for the development of novel antibiotics. However, to date, the signaling mechanism of YycG and its stimulus are poorly understood mainly because of a lack of structural information on YycG...
July 31, 2016: Journal of Molecular Biology
Aizhen Xiong, Artemis Lu Yan, Cathy W C Bi, Kelly Y C Lam, Gallant K L Chan, Kitty K M Lau, Tina T X Dong, Huangquan Lin, Li Yang, Zhengtao Wang, Karl W K Tsim
BACKGROUND: Pyrrolizidine alkaloids (PAs) are commonly found in many plants including those used in medical therapeutics. The hepatotoxicities of PAs have been demonstrated both in vivo and in vitro; however, the neurotoxicities of PAs are rarely mentioned. PURPOSE: In this study, we aimed to investigate in vitro neurotoxicities of clivorine, one of the PAs found in various Ligularia species, in cultured PC12 cells. STUDY DESIGN: PC12 cell line was employed to first elucidate the neurotoxicity and the underlying mechanism of clivorine, including cell viability and morphology change, neuronal differentiation marker and signaling pathway...
August 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Xianhui Xie, Zhengsheng Li, Mingjing Pi, Jing Wu, Wen Zeng, Li Zuo, Yan Zha
Objective To investigate the effect of 1, 25-(OH)2-VD3 on collagen type III (Col3), collagen type IV (Col4) and p38 mitogen-activated protein kinase (p38 MAPK) in rat models of type 2 diabetic nephropathy, and explore the relationships of p38MAPK with Col3 and Col4. Methods Rat models of type 2 diabetic nephropathy were induced by streptozocin (STZ, 30 mg/kg) combined with high-glucose-and-fat diet. Sixty rats were randomly divided into control group, model group, 1, 25-(OH)2-VD3 treatment group [given 1, 25-(OH)2-VD3 6 ng/(100 g...
July 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Francesca Semplici, Angeles Mondragon, Benedict Macintyre, Katja Madeyski-Bengston, Anette Persson-Kry, Sara Barr, Anna Ramne, Anna Marley, James McGinty, Paul French, Helen Soedling, Ryohsuke Yokosuka, Julien Gaitan, Jochen Lang, Stephanie Migrenne-Li, Erwann Philippe, Pedro L Herrera, Christophe Magnan, Gabriela da Silva Xavier, Guy A Rutter
AIMS/HYPOTHESIS: Per-Arnt-Sim kinase (PASK) is a nutrient-regulated domain-containing protein kinase previously implicated in the control of insulin gene expression and glucagon secretion. Here, we explore the roles of PASK in the control of islet hormone release, by generating mice with selective deletion of the Pask gene in pancreatic beta or alpha cells. METHODS: Floxed alleles of Pask were produced by homologous recombination and animals bred with mice bearing beta (Ins1 (Cre); PaskBKO) or alpha (Ppg (Cre) [also known as Gcg]; PaskAKO) cell-selective Cre recombinase alleles...
September 2016: Diabetologia
Sean R Stevenson, Yasuko Kamisugi, Chi H Trinh, Jeremy Schmutz, Jerry W Jenkins, Jane Grimwood, Wellington Muchero, Gerald A Tuskan, Stefan A Rensing, Daniel Lang, Ralf Reski, Michael Melkonian, Carl J Rothfels, Fay-Wei Li, Anders Larsson, Gane K-S Wong, Thomas A Edwards, Andrew C Cuming
The anatomically simple plants that first colonized land must have acquired molecular and biochemical adaptations to drought stress. Abscisic acid (ABA) coordinates responses leading to desiccation tolerance in all land plants. We identified ABA nonresponsive mutants in the model bryophyte Physcomitrella patens and genotyped a segregating population to map and identify the ABA NON-RESPONSIVE (ANR) gene encoding a modular protein kinase comprising an N-terminal PAS domain, a central EDR domain, and a C-terminal MAPKKK-like domain...
June 2016: Plant Cell
Can Wei, Hongzhu Li, Yuehong Wang, Xue Peng, Hongjiang Shao, Hongxia Li, Shuzhi Bai, Changqing Xu
Myocardial infarction (MI) is associated with a high mortality rate, which is attributed to the effects of myocyte loss that occurs as a result of ischemia-induced cell death. Very few therapies can effectively prevent or delay the effects of ischemia. Polyamines (PAs) are polycations required for cell growth and division, and their use may prevent cell loss. The aim of this study was to investigate the relationship between hypoxia/ischemia (H/I)-induced cell apoptosis and PA metabolism and to investigate the ability of spermine to limit H/I injury in cardiomyocytes by blocking the mitochondrial apoptotic pathway...
August 2016: Experimental Biology and Medicine
Xiuhong Yang, Yaqiu Li, Congcong Feng, Lili Guo, Huimin Jin
OBJECTIVE: To explore the renoprotective effects of (-)-epigallocatechin-3-gallate (EGCG) and its potential mechanism in type 2 diabetic db/db mice. METHODS: 8-week-old db/db mice (6 h fasting plasma glucose >16.7 mmol/L) were allocated randomly into Control group (non-intervention group, n=8), EGCG A group (50 mg·kg(-1)·d(-1,)n=8), EGCG B group (100 mg·kg(-1)·d(-1,)n=8). Before the study and after the intervention (in the 4(th)and 8(th)week), the body weight, the level of fasting plasma glucose, oral glucose tolerance test (OGTT) were measured and 24 h urine samples were collected...
May 10, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Ah-Young Shin, Yun-Jeong Han, Ayoung Baek, Taeho Ahn, Soo Young Kim, Thai Son Nguyen, Minky Son, Keun Woo Lee, Yu Shen, Pill-Soon Song, Jeong-Il Kim
It has been suggested that plant phytochromes are autophosphorylating serine/threonine kinases. However, the biochemical properties and functional roles of putative phytochrome kinase activity in plant light signalling are largely unknown. Here, we describe the biochemical and functional characterization of Avena sativa phytochrome A (AsphyA) as a potential protein kinase. We provide evidence that phytochrome-interacting factors (PIFs) are phosphorylated by phytochromes in vitro. Domain mapping of AsphyA shows that the photosensory core region consisting of PAS-GAF-PHY domains in the N-terminal is required for the observed kinase activity...
2016: Nature Communications
Tatiana V Kudryashova, Dmitry A Goncharov, Andressa Pena, Neil Kelly, Rebecca Vanderpool, Jeff Baust, Ahasanul Kobir, William Shufesky, Ana L Mora, Adrian E Morelli, Jing Zhao, Kaori Ihida-Stansbury, Baojun Chang, Horace DeLisser, Rubin M Tuder, Steven M Kawut, Herman Hw Silljé, Steven Shapiro, Yutong Zhao, Elena A Goncharova
RATIONALE: Enhanced proliferation and impaired apoptosis of pulmonary arterial vascular smooth muscle cells (PAVSMC) are key pathophysiological components of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). OBJECTIVES: To determine the role and therapeutic relevance of HIPPO signaling in PAVSMC proliferation/apoptosis imbalance in PAH. MEASUREMENTS AND MAIN RESULTS: Immunohistochemical and immunoblot analyses demonstrated that the HIPPO central component large tumor suppressor 1 (LATS1) is inactivated in small remodeled pulmonary arteries (PAs) and distal PAVSMC in idiopathic PAH...
April 27, 2016: American Journal of Respiratory and Critical Care Medicine
Thomas H Mann, W Seth Childers, Jimmy A Blair, Michael R Eckart, Lucy Shapiro
All cells must integrate sensory information to coordinate developmental events in space and time. The bacterium Caulobacter crescentus uses two-component phospho-signalling to regulate spatially distinct cell cycle events through the master regulator CtrA. Here, we report that CckA, the histidine kinase upstream of CtrA, employs a tandem-PAS domain sensor to integrate two distinct spatiotemporal signals. Using CckA reconstituted on liposomes, we show that one PAS domain modulates kinase activity in a CckA density-dependent manner, mimicking the stimulation of CckA kinase activity that occurs on its transition from diffuse to densely packed at the cell poles...
2016: Nature Communications
Yuchen Feng, Steven K Backues, Misuzu Baba, Jin-mi Heo, J Wade Harper, Daniel J Klionsky
Macroautophagy is primarily a degradative process that cells use to break down their own components to recycle macromolecules and provide energy under stress conditions, and defects in macroautophagy lead to a wide range of diseases. Atg9, conserved from yeast to mammals, is the only identified transmembrane protein in the yeast core macroautophagy machinery required for formation of the sequestering compartment termed the autophagosome. This protein undergoes dynamic movement between the phagophore assembly site (PAS), where the autophagosome precursor is nucleated, and peripheral sites that may provide donor membrane for expansion of the phagophore...
2016: Autophagy
Thimo Wiewelhove, Christian Raeder, Tim Meyer, Michael Kellmann, Mark Pfeiffer, Alexander Ferrauti
PURPOSE: To investigate the effect of repeated use of active recovery during a four-day shock microcycle with seven high-intensity interval training (HIT) sessions on markers of fatigue. METHODS: Eight elite male junior tennis players (age: 15.1±1.4 years) with an international ranking between 59 and 907 (International Tennis Federation) participated in this study. After each training session, the players completed 15 min of either moderate jogging (active recovery, ACT) or passive recovery (PAS) with a crossover design, which was interrupted by a four-month washout period...
March 21, 2016: International Journal of Sports Physiology and Performance
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