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PASK kinase

Ana Pérez-García, Pilar Dongil, Verónica Hurtado-Carneiro, Enrique Blázquez, Carmen Sanz, Elvira Álvarez
The prevalence of overweight and obesity in the population, along with their associated complications, is a major factor contributing to increased morbidity and mortality in developed countries. The liver is a vital organ for maintaining metabolic homeostasis, especially in the adjustment periods in fasting and feeding. Per-Arnt-Sim (PAS) kinase (PASK) controls glucose homeostasis and energy metabolism in response to nutritional status. PASK-deficient mice with a high-fat diet (HFD) resist the development of obesity and hepatic steatosis, with improved insulin sensitivity...
March 12, 2018: Journal of Nutritional Biochemistry
Dóra Marosvári, Noémi Nagy, Csilla Kriston, Beáta Deák, Melinda Hajdu, Csaba Bödör, Irén Csala, Attila G Bagó, Zoltán Szállási, Anna Sebestyén, Lilla Reiniger
The primary aim of this study was to determine mTOR-pathway activity in primary central nervous system lymphoma (PCNSL), which could be a potential target for therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity, we aimed to identify other pathways that may lead to S6 phosphorylation. We measured mTOR activity with immunohistochemistry for p-mTOR and its downstream effectors p(T389)-p70S6K1, p-S6, and p-4E-BP1 in 31 cases of PCNSL and 51 cases of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6 phosphorylation pathways with p-RSK, p(T229)-p70S6K1, and PASK antibodies...
April 1, 2018: Journal of Neuropathology and Experimental Neurology
Ming Bai, Yifang Liu, Dechang Yin, Mingzi Zhang, Youbin Wang, Xuemei Ma, Yunqi Liu, Pengxiang Zhao
BACKGROUND: The goals of this study were to validate the role of c-Jun N-terminal kinase (JNK) activation in skin flap apoptosis in a rat model of abdomen skin ischemia and/or reperfusion (IR) and to compare the protective effect of SP600125 and hydrogen-rich saline in skin IR injury. METHODS: Male Sprague-Dawley rats were divided into five groups: one sham surgery group and four surgery groups. Before undergoing 3 h of IR management, the surgery groups were treated with normal saline (IR), dimethyl sulfoxide, SP600125 (SP), and hydrogen-rich saline (H)...
December 2016: Journal of Surgical Research
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...
September 23, 2016: ELife
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
Dan-Dan Zhang, Ji-Gang Zhang, Xin Wu, Ying Liu, Sheng-Ying Gu, Guan-Hua Zhu, Yu-Zhu Wang, Gao-Lin Liu, Xiao-Yu Li
Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease associated with lipotoxicity, lipid peroxidation, oxidative stress, and inflammation. Nuciferine, an active ingredient extracted from the natural lotus leaf, has been reported to be effective for the prevention and treatment of NAFLD. Per-Arnt-Sim kinase (PASK) is a nutrient responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, and gene expression. The aim of the present study was to investigate the protective effect of nuciferine against NAFLD and its inhibitory effect on PASK, exploring the possible underlying mechanism of nuciferine-mediated inhibition on NAFLD...
2015: Frontiers in Pharmacology
Dan-dan Zhang, Ji-gang Zhang, Yu-zhu Wang, Ying Liu, Gao-lin Liu, Xiao-yu Li
Per-Arnt-Sim Kinase (PASK) is an evolutionarily-conserved nutrient-responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, phosphorylation, and gene expression. Recent data suggests that mammalian PAS kinase is involved in glucose metabolism and acts on pancreatic islet α/β cells and glycogen synthase (GS), affecting insulin secretion and blood glucose levels. In addition, PASK knockout mice (PASK-/-) are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet, implying that PASK may be a new target for metabolic syndrome (MetS) treatment as well as the cellular nutrients and energy sensors-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the targets of rapamycin (m-TOR)...
September 2015: Nutrients
Yi-Ding Xiao, Yun-Qi Liu, Jia-La Li, Xue-Mei Ma, You-Bin Wang, Yi-Fang Liu, Ming-Zi Zhang, Peng-Xiang Zhao, Fei Xie, Zi-Xuan Deng
BACKGROUND: Hyperbaric oxygen (HBO) improves skin flap function and inhibits partial necrosis induced by ischemia-reperfusion (I/R) injury. Our study aimed to evaluate the mechanism underlying HBO regulation of the antiapoptosis factors associated with I/R injury of skin flaps. METHODS: The rats were divided into sham surgery, I/R, and HBO groups. Rats from the HBO group received HBO preconditioning followed by I/R surgery. Blood perfusion of the skin flaps was measured with laser Doppler flowmeters...
December 2015: Journal of Surgical Research
Yun-Qi Liu, Yi-Fang Liu, Xue-Mei Ma, Yi-Ding Xiao, You-Bin Wang, Ming-Zi Zhang, Ai-Xin Cheng, Ting-Ting Wang, Jia-La Li, Peng-Xiang Zhao, Fei Xie, Xin Zhang
INTRODUCTION: Many pathways have been reported involving the effect of hydrogen-rich saline on protecting skin flap partial necrosis induced by the inflammation of ischemia/reperfusion injury. This study focused on the influence of hydrogen-rich saline treatment on apoptosis pathway of ASK-1/JNK and Bcl-2/Bax radio in I/R injury of skin flaps. METHODS: Adult male Sprague-Dawley rats were divided into three groups. Group 1 was sham surgery group, Group 2 and 3 were ischemia/reperfusion surgery treated with physiological saline and hydrogen-rich saline respectively...
July 2015: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
Xiaoying Wu, Donna Romero, Wojciech I Swiatek, Irene Dorweiler, Chintan K Kikani, Hana Sabic, Ben S Zweifel, John McKearn, Jeremy T Blitzer, G Allen Nickols, Jared Rutter
Elevated hepatic synthesis of fatty acids and triglycerides, driven by hyperactivation of the SREBP-1c transcription factor, has been implicated as a causal feature of metabolic syndrome. SREBP-1c activation requires the proteolytic maturation of the endoplasmic-reticulum-bound precursor to the active, nuclear transcription factor, which is stimulated by feeding and insulin signaling. Here, we show that feeding and insulin stimulate the hepatic expression of PASK. We also demonstrate, using genetic and pharmacological approaches, that PASK is required for the proteolytic maturation of SREBP-1c in cultured cells and in the mouse and rat liver...
July 10, 2014: Cell Reports
Juan Li, David G Kent, Anna L Godfrey, Harriet Manning, Jyoti Nangalia, Athar Aziz, Edwin Chen, Kourosh Saeb-Parsy, Juergen Fink, Rachel Sneade, Tina L Hamilton, Dean C Pask, Yvonne Silber, Xiaodong Zhao, Cedric Ghevaert, Pentao Liu, Anthony R Green
Genomic regions of acquired uniparental disomy (UPD) are common in malignancy and frequently harbor mutated oncogenes. Homozygosity for such gain-of-function mutations is thought to modulate tumor phenotype, but direct evidence has been elusive. Polycythemia vera (PV) and essential thrombocythemia (ET), 2 subtypes of myeloproliferative neoplasms, are associated with an identical acquired JAK2V617F mutation but the mechanisms responsible for distinct clinical phenotypes remain unclear. We provide direct genetic evidence and demonstrate that homozygosity for human JAK2V617F in knock-in mice results in a striking phenotypic switch from an ET-like to PV-like phenotype...
May 15, 2014: Blood
Verónica Hurtado-Carneiro, Isabel Roncero, Sascha S Egger, Roland H Wenger, Enrique Blazquez, Carmen Sanz, Elvira Alvarez
The complications caused by overweight, obesity and type 2 diabetes are one of the main problems that increase morbidity and mortality in developed countries. Hypothalamic metabolic sensors play an important role in the control of feeding and energy homeostasis. PAS kinase (PASK) is a nutrient sensor proposed as a regulator of glucose metabolism and cellular energy. The role of PASK might be similar to other known metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR)...
October 2014: Molecular Neurobiology
Desiree DeMille, Julianne H Grose
Per-Arnt-Sim (PAS) kinase (PASK, PASKIN, and PSK) is a member of the group of nutrient sensing protein kinases. These protein kinases sense the energy or nutrient status of the cell and regulate cellular metabolism appropriately. PAS kinase responds to glucose availability and regulates glucose homeostasis in yeast, mice, and man. Despite this pivotal role, the molecular mechanisms of PAS kinase regulation and function are largely unknown. This review focuses on what is known about PAS kinase, including its conservation from yeast to man, identified substrates, associated phenotypes and role in metabolic disease...
November 2013: IUBMB Life
Meriem Semache, Bader Zarrouki, Ghislaine Fontés, Sarah Fogarty, Chintan Kikani, Mohammad B Chawki, Jared Rutter, Vincent Poitout
In pancreatic β-cells, glucose induces the binding of the transcription factor pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate insulin gene transcription. At low glucose levels, glycogen synthase kinase 3β (GSK3β) is known to phosphorylate PDX-1 on C-terminal serine residues, which triggers PDX-1 proteasomal degradation. We previously showed that the serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin gene transcription via PDX-1. However, the mechanisms underlying this regulation are unknown...
August 23, 2013: Journal of Biological Chemistry
Verónica Hurtado-Carneiro, Isabel Roncero, Enrique Blazquez, Elvira Alvarez, Carmen Sanz
PAS kinase (PASK) is a nutrient sensor that is highly conserved throughout evolution. PASK-deficient mice reveal a metabolic phenotype similar to that described in S6 kinase-1 S6K1-deficient mice that are protected against obesity. Hypothalamic metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR), play an important role in feeding behavior, the homeostasis of body weight, and energy balance. These sensors respond to changes in nutrient levels in the hypothalamic areas involved in feeding behavior and in neuroblastoma N2A cells, and we have recently reported that those effects are modulated by the anorexigenic peptide glucagon-like peptide-1 (GLP-1)...
December 2013: Molecular Neurobiology
David G Kent, Juan Li, Hinal Tanna, Juergen Fink, Kristina Kirschner, Dean C Pask, Yvonne Silber, Tina L Hamilton, Rachel Sneade, Benjamin D Simons, Anthony R Green
Recent descriptions of significant heterogeneity in normal stem cells and cancers have altered our understanding of tumorigenesis, emphasizing the need to understand how single stem cells are subverted to cause tumors. Human myeloproliferative neoplasms (MPNs) are thought to reflect transformation of a hematopoietic stem cell (HSC) and the majority harbor an acquired V617F mutation in the JAK2 tyrosine kinase, making them a paradigm for studying the early stages of tumor establishment and progression. The consequences of activating tyrosine kinase mutations for stem and progenitor cell behavior are unclear...
2013: PLoS Biology
Thomas M Moon, Fernando Correa, Lisa N Kinch, Alexander T Piala, Kevin H Gardner, Elizabeth J Goldsmith
WNK1 [with no lysine (K)-1] is a 250-kDa serine/threonine protein kinase involved in the maintenance of cellular salt levels and is directly linked to a hereditary form of hypertension. Here, we report the solution NMR structure of the autoinhibitory domain of WNK1 (WNK1-AI), a small regulatory subunit that lies immediately C-terminal of the kinase domain. We show that this domain is a homolog of the RFXV-binding PASK/FRAY homology 2 (PF2) domain found in OSR (oxidative stress responsive) and SPAK (serine/threonine proline-alanine-rich) kinases, which are substrates of WNK1...
April 26, 2013: Journal of Molecular Biology
Caleb M Cardon, Thomas Beck, Michael N Hall, Jared Rutter
In Saccharomyces cerevisiae, phosphorylation of Ugp1 by either of the yeast PASK family protein kinases (yPASK), Psk1 or Psk2, directs this metabolic enzyme to deliver glucose to the periphery for synthesis of the cell wall. However, we isolated PSK1 and PSK2 in a high-copy suppressor screen of a temperature-sensitive mutant of target of rapamycin 2 (TOR2). Posttranslational activation of yPASK, either by cell integrity stress or by growth on nonfermentative carbon sources, also suppressed the growth defect resulting from tor2 mutation...
January 31, 2012: Science Signaling
Francesca Semplici, Martine Vaxillaire, Sarah Fogarty, Meriem Semache, Amélie Bonnefond, Ghislaine Fontés, Julien Philippe, Gargi Meur, Frederique Diraison, Richard B Sessions, Jared Rutter, Vincent Poitout, Philippe Froguel, Guy A Rutter
PAS kinase (PASK) is a glucose-regulated protein kinase involved in the control of pancreatic islet hormone release and insulin sensitivity. We aimed here to identify mutations in the PASK gene that may be associated with young-onset diabetes in humans. We screened 18 diabetic probands with unelucidated maturity-onset diabetes of the young (MODY). We identified two rare nonsynonymous mutations in the PASK gene (p.L1051V and p.G1117E), each of which was found in a single MODY family. Wild type or mutant PASKs were expressed in HEK 293 cells...
December 23, 2011: Journal of Biological Chemistry
Florian Lang, Susanne Ullrich, Erich Gulbins
INTRODUCTION: Ceramide may be synthesized de novo or generated by sphingomyelinase-dependent hydrolysis of sphingomyelin. AREAS COVERED: The role of ceramide, ceramide-sensitive signaling and ion channels in β-cell apoptosis, lipotoxicity and amyloid-induced β-cell death. EXPERT OPINION: Ceramide participates in β-cell dysfunction and apoptosis after exposure to TNFα, IL-1β and IFN-γ, excessive amyloid and islet amyloid polypeptide or non-esterified fatty acids (lipotoxicity)...
September 2011: Expert Opinion on Therapeutic Targets
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