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PAS kinase

Charles E Norton, Steven S Segal
The sensory neurotransmitter calcitonin gene-related peptide (CGRP) is associated with vasodilation of systemic arteries through activation of ATP-sensitive potassium channels (KATP) in smooth muscle cells (SMCs), however its effects on endothelial cell (EC) membrane potential (Vm) are unresolved. In pulmonary arteries (PAs) of C57BL/6J mice, we questioned whether CGRP would hyperpolarize ECs as well as SMCs. Intact PAs were isolated and immunostained for CGRP to confirm sensory innervation; vessel segments (length, 1-2 mm; diameter ∼150 µm) with intact or denuded endothelium were cannulated and pressurized to 16 cm H2O at 37{degree sign}C...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Mary G Lin, Johannes Schöneberg, Christopher W Davies, Xuefeng Ren, James H Hurley
Yeast macroautophagy begins with the de novo formation of a double membrane phagophore at the preautophagosomal structure (PAS), followed by its expansion into the autophagosome responsible for cargo engulfment. The kinase Atg1 is recruited to the PAS by Atg13 through interactions between the EAT domain of the former and the tMIM motif of the latter. Mass spectrometry data has shown that in the absence of Atg13, the EAT domain structure is strikingly dynamic, but the function of this Atg13-free dynamic state has been unclear...
March 14, 2018: Molecular Biology of the Cell
Unni K Samavedam, Nina Mitschker, Anika Kasprick, Katja Bieber, Enno Schmidt, Tamás Laskay, Andreas Recke, S Goletz, Gestur Vidarsson, Franziska S Schulze, Mikko Armbrust, Katharina Schulze Dieckhoff, Hendri H Pas, Marcel F Jonkman, Kathrin Kalies, Detlef Zillikens, Yask Gupta, Saleh M Ibrahim, Ralf J Ludwig
Because of the morbidity and limited therapeutic options of autoimmune diseases, there is a high, and thus far, unmet medical need for development of novel treatments. Pemphigoid diseases, such as epidermolysis bullosa acquisita (EBA), are prototypical autoimmune diseases that are caused by autoantibodies targeting structural proteins of the skin, leading to inflammation, mediated by myeloid cells. To identify novel treatment targets, we performed cutaneous genome-wide mRNA expression profiling in 190 outbred mice after EBA induction...
2018: Frontiers in Immunology
Elodie Lesne, Elian Dupré, Marc F Lensink, Camille Locht, Rudy Antoine, Françoise Jacob-Dubuisson
Bordetella pertussis controls the expression of its virulence regulon through the two-component system BvgAS. BvgS is a prototype for a family of multidomain sensor kinases. In BvgS, helical linkers connect periplasmic Venus flytrap (VFT) perception domains to a cytoplasmic Per-Arnt-Sim (PAS) domain and the PAS domain to the dimerization/histidine phosphotransfer (DHp) domain of the kinase. The two linkers can adopt coiled-coil structures but cannot do so simultaneously. The first linker forms a coiled coil in the kinase mode and the second in the phosphatase mode, with the other linker in both cases showing an increase in dynamic behavior...
February 27, 2018: MBio
Xuan Zhou, Nan Zhang, Liming Xia, Qing Li, Jiahui Shao, Qirong Shen, Ruifu Zhang
Efficient biofilm formation and root colonization capabilities facilitate the ability of beneficial plant rhizobacteria to promote plant growth and antagonize soil-borne pathogens. Biofilm formation by plant-beneficial Bacillus strains is triggered by environmental cues, including oxygen deficiency, but the pathways that sense these environmental signals and regulate biofilm formation have not been thoroughly elucidated. In this study, we showed that the ResDE two-component regulatory system in the plant growth-promoting rhizobacterium Bacillus amyloliquefaciens SQR9 senses the oxygen deficiency signal and regulates biofilm formation...
February 2, 2018: Applied and Environmental Microbiology
Nicholas Ting Xun Ong, Jeffrey J Tabor
Genetically-engineered photoreceptors enable unrivaled control over gene expression. Previously, we ported the Synechocystis PCC 6803 CcaSR two-component system, which is activated by green light and de-activated by red, into E. coli, resulting in a sensor with 6-fold dynamic range. Later, we optimized pathway protein expression levels and the output promoter sequence to decrease transcriptional leakiness and increase the dynamic range to approximately 120-fold. These CcaSR v1.0 and 2.0 systems have been used for precise quantitative, temporal, and spatial control of gene expression for a variety of applications...
February 8, 2018: Chembiochem: a European Journal of Chemical Biology
Vishal R Yadav, Tengyao Song, Lin Mei, Leroy Joseph, Yun-Min Zheng, Yong-Xiao Wang
Hypoxia-induced pulmonary vasoconstriction (HPV) is attributed to an increase in intracellular Ca2+ concentration ([Ca2+]i) in pulmonary artery smooth muscle cells (PASMCs). We have reported that phospholipase C-γ1 (PLCγ1) plays a significant role in the hypoxia-induced increase in [Ca2+]i in PASMCs and attendant HPV. In this study, we intended to determine molecular mechanisms for hypoxic Ca2+ and contractile responses in PASMCs. Our data reveal that hypoxic vasoconstriction occurs in PAs, but not in mesenteric arteries (MAs)...
February 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
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...
January 19, 2018: Journal of Neuropathology and Experimental Neurology
Samrat Roy, M K Mathew
Fluid movement within the heart generates substantial shear forces, but the effect of this mechanical stress on the electrical activity of the human heart has not been examined. The fast component of the delayed rectifier potassium currents responsible for repolarization of the cardiac action potential, Ikr, is encoded by the hERG channel. Here, we exposed hERG1a channel-expressing HEK293T cells to laminar shear stress (LSS) and observed that this mechanical stress increased the whole-cell current by 30%-40%...
January 5, 2018: Journal of Biological Chemistry
Corina Marziano, Kwangseok Hong, Eric L Cope, Michael I Kotlikoff, Brant E Isakson, Swapnil K Sonkusare
BACKGROUND: Recent studies demonstrate that spatially restricted, local Ca2+ signals are key regulators of endothelium-dependent vasodilation in systemic circulation. There are drastic functional differences between pulmonary arteries (PAs) and systemic arteries, but the local Ca2+ signals that control endothelium-dependent vasodilation of PAs are not known. Localized, unitary Ca2+ influx events through transient receptor potential vanilloid 4 (TRPV4) channels, termed TRPV4 sparklets, regulate endothelium-dependent vasodilation in resistance-sized mesenteric arteries via activation of Ca2+-dependent K+ channels...
December 23, 2017: Journal of the American Heart Association
Gianluca Bagnato, Natasha Irrera, Gabriele Pizzino, Domenico Santoro, William Neal Roberts, Gianfilippo Bagnato, Giovanni Pallio, Mario Vaccaro, Francesco Squadrito, Antonino Saitta, Domenica Altavilla, Alessandra Bitto
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibroblast activation and fibrosis of the skin and internal organs. Alterations in cell-integrin interaction are sufficient to initiate pro-fibrotic processes. SSc fibroblasts express both αvβ3 and αvβ5 integrins and their activation induces myofibroblasts differentiation. The aim of this study was to evaluate the effect of the anb3 and anb5 inhibitor, cilengitide, on the development of vascular and fibrotic changes in the chronic oxidant stress murine model of systemic sclerosis...
December 13, 2017: Clinical Science (1979-)
Fiona Blackhall, D Ross Camidge, Alice T Shaw, Jean-Charles Soria, Benjamin J Solomon, Tony Mok, Vera Hirsh, Pasi A Jänne, Yuankai Shi, Pan-Chyr Yang, Tommaso De Pas, Toyoaki Hida, Javier De Castro Carpeño, Silvana Lanzalone, Anna Polli, Shrividya Iyer, Arlene Reisman, Keith D Wilner, Dong-Wan Kim
Purpose: Crizotinib is a potent, orally administered tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). We report final results from PROFILE 1005, the largest clinical trial to date for an ALK inhibitor in ALK-positive NSCLC. Patients and methods: PROFILE 1005 (NCT00932451) was a multicenter, single-arm phase 2 trial of the efficacy, safety and tolerability of crizotinib (250 mg twice daily; 3 week continuous treatment cycles) in patients with ALK-positive NSCLC after failure of ≥1 lines of systemic treatment for locally advanced/metastatic disease...
2017: ESMO Open
Zhou Li, Yan Zhang, Dandan Peng, Yan Peng, Xinquan Zhang, Xiao Ma, Linkai Huang, Yanhong Yan
Changes of endogenous polyamine (PA) levels could be a key adaptive response to drought in plants. White clover pretreated with or without dicyclohexylamine (DCHA), an inhibitor of PA biosynthesis, was subjected to drought stress induced by 18% polyethylene glycol 6000 for 8 days in controlled growth chambers. Results showed that drought stress significantly increased endogenous PA content, whereas DCHA significantly decreased PA accumulation under drought stress. The attenuate PA biosynthesis was unfavorable for plant growth and drought tolerance, as reflected by significantly lower relative water content, relative growth rate, instantaneous water use efficiency, and cell membrane stability in leaves in response to drought...
November 28, 2017: Protoplasma
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
Maura Rojas-Pirela, Daniel J Rigden, Paul A Michels, Ana J Cáceres, Juan Luis Concepción, Wilfredo Quiñones
Per-ARNT-Sim (PAS) domains of proteins play important roles as modules for signalling and cellular regulation processes in widely diverse organisms such as Archaea, Bacteria, protists, plants, yeasts, insects and vertebrates. These domains are present in many proteins where they are used as sensors of stimuli and modules for protein interactions. Characteristically, they can bind a broad spectrum of molecules. Such binding causes the domain to trigger a specific cellular response or to make the protein containing the domain susceptible to responding to additional physical or chemical signals...
January 2018: Molecular and Biochemical Parasitology
Evangelos D Michelakis, Vikram Gurtu, Linda Webster, Gareth Barnes, Geoffrey Watson, Luke Howard, John Cupitt, Ian Paterson, Richard B Thompson, Kelvin Chow, Declan P O'Regan, Lan Zhao, John Wharton, David G Kiely, Adam Kinnaird, Aristeidis E Boukouris, Chris White, Jayan Nagendran, Darren H Freed, Stephen J Wort, J Simon R Gibbs, Martin R Wilkins
Pulmonary arterial hypertension (PAH) is a progressive vascular disease with a high mortality rate. It is characterized by an occlusive vascular remodeling due to a pro-proliferative and antiapoptotic environment in the wall of resistance pulmonary arteries (PAs). Proliferating cells exhibit a cancer-like metabolic switch where mitochondrial glucose oxidation is suppressed, whereas glycolysis is up-regulated as the major source of adenosine triphosphate production. This multifactorial mitochondrial suppression leads to inhibition of apoptosis and downstream signaling promoting proliferation...
October 25, 2017: Science Translational Medicine
Jing Xiong, Wen-Qu Zhao, Guo-Hua Huang, Li-Hong Yao, Hang-Ming Dong, Chang-Hui Yu, Hai-Jin Zhao, Shao-Xi Cai
OBJECTIVE: To explore the role of the receptor for advanced glycation end products (RAGE) in regulating the expression of MUC5AC and mucus production in a mouse model of toluene diisocyanate (TDI)?induced asthma. METHODS: BALB/c mice were randomly divided into control group, vehicle (AOO) group, TDI?induced asthma group and RAGE inhibitor (FPS?ZM1) group. PAS staining, Western blotting, and immunohistochemistry were used to analyze the changes in mucus production and MUC5AC expression in the airway of the mice, and the expression of p?ERK was detected with Western blotting...
October 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
E Sethe Burgie, Adam N Bussell, Shu-Hui Lye, Tong Wang, Weiming Hu, Katrice E McLoughlin, Erin L Weber, Huilin Li, Richard D Vierstra
Phytochromes (Phys) encompass a diverse collection of bilin-containing photoreceptors that help plants and microorganisms perceive light through photointerconversion between red light (Pr) and far-red light (Pfr)-absorbing states. In addition, Pfr reverts thermally back to Pr via a highly enthalpic process that enables temperature sensation in plants and possibly other organisms. Through domain analysis of the Arabidopsis PhyB isoform assembled recombinantly, coupled with measurements of solution size, photoconversion, and thermal reversion, we identified both proximal and distal features that influence all three metrics...
October 20, 2017: Scientific Reports
Shuya Kasai, Mary J E Richardson, Satoru Torii, Ken-Ichi Yasumoto, Hiroki Shima, Kazuhiko Igarashi, Ken Itoh, Kazuhiro Sogawa, Kazutaka Murayama
Inhibitory PAS domain protein (IPAS) is a bifunctional protein that downregulates hypoxic gene expression and exerts proapoptotic activity by preventing prosurvival activity of Bcl-xL and its related factors. Proapoptotic activity of IPAS is attenuated by the activation of the PINK1-Parkin pathway, and involved in neuronal degeneration in an experimental mouse model of Parkinson's disease. The current study shows that phosphorylation of IPAS at Ser184 by MAPK-activated protein kinase 2 (MK2 or MAPKAPK2) enhances the proapoptotic function of IPAS...
December 2017: FEBS Journal
Yuriko Yasuda-Onozawa, Osamu Handa, Yuji Naito, Chihiro Ushiroda, Yosuke Suyama, Yuki Toyokawa, Takaaki Murakami, Tomoyo Yasuda, Tomohiro Ueda, Atsushi Majima, Yuma Hotta, Toshifumi Doi, Makoto Tanaka, Yusuke Horii, Yasuki Higashimura, Katsura Mizushima, Mayuko Morita, Yukiko Uehara, Hideki Horie, Akifumi Fukui, Osamu Dohi, Tetsuya Okayama, Naohisa Yoshida, Kazuhiro Kamada, Kazuhiro Katada, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Hideyuki Konishi, Yoshito Itoh
Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet cell‑like cells...
December 2017: Molecular Medicine Reports
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