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phosphatase protein 1

Hye-Jin Park, Kang-Woo Lee, Eun S Park, Stephanie Oh, Run Yan, Jie Zhang, Thomas G Beach, Charles H Adler, Michael Voronkov, Steven P Braithwaite, Jeffry B Stock, M Maral Mouradian
OBJECTIVE: Protein phosphatase 2A (PP2A) is a heterotrimeric holoenzyme composed of a catalytic C subunit, a structural A subunit, and one of several regulatory B subunits that confer substrate specificity. The assembly and activity of PP2A are regulated by reversible methylation of the C subunit. α-Synuclein, which aggregates in Parkinson disease (PD) and dementia with Lewy bodies (DLB), is phosphorylated at Ser129, and PP2A containing a B55α subunit is a major phospho-Ser129 phosphatase...
October 2016: Annals of Clinical and Translational Neurology
J Xu, B J Hartley, P Kurup, A Phillips, A Topol, M Xu, C Ononenyi, E Foscue, S-M Ho, T D Baguley, N Carty, C S Barros, U Müller, S Gupta, P Gochman, J Rapoport, J A Ellman, C Pittenger, B Aronow, A C Nairn, M W Nestor, P J Lombroso, K J Brennand
The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1(+/-) knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1(+/-) mice...
October 18, 2016: Molecular Psychiatry
Joyce Bischoff, Guillem Casanovas, Jill Wylie-Sears, Dae-Hee Kim, Philipp Bartko, J Guerrero, Jacob Dal-Bianco, Jonathan Beaudoin, Michael Garcia, Suzanne Sullivan, Margo Seybolt, Brittan Morris, Joshua Keegan, Whitney Irvin, Elena Aikawa, Robert Levine
RATIONALE: Ischemic mitral regurgitation (IMR), a complication after myocardial infarction (MI), induces adaptive mitral valve (MV) responses that may be initially beneficial, but eventually lead to leaflet fibrosis and MV dysfunction. We sought to examine the MV endothelial response and its potential contribution to IMR. OBJECTIVE: Endothelial, interstitial and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post-MI, was analyzed in vitro...
October 6, 2016: Circulation Research
Ling Nie, Jing-Hong Zhao, Jiang Wang, Rong Song, Shan-Jun Zhu
Cardiac fibroblasts (CFs) play a key role in cardiac fibrosis by regulating the balance between extracellular matrix synthesis and breakdown. Although phosphatase and tensin homologue on chromosome 10 (PTEN) has been found to play an important role in cardiovascular disease, it is not clear whether PTEN is involved in functional regulation of CFs. In the present study, PTEN was overexpressed in neonatal rat CFs via recombinant adenovirus-mediated gene transfer. The effects of PTEN overexpression on cell-cycle progression and angiotensin II- (Ang II-) mediated regulation of collagen metabolism, synthesis of matrix metalloproteinases, and Akt/P27 signaling were investigated...
2016: BioMed Research International
Motasem Melhem, Mohamed Abu-Farha, Dinu Antony, Ashraf Al Madhoun, Chiara Bacchelli, Fadi Alkayal, Irina AlKhairi, Sumi John, Mohamad Alomari, Phillip L Beales, Osama Alsmadi
OBJECTIVE: To characterize the underlying genetic and molecular defects in a consanguineous family with life-long blood disorder manifested with thrombocytopenia (low platelets count) and anemia. METHODS: Genetic linkage analysis, exome sequencing and functional genomics were carried out to identify and characterize the defective gene. RESULTS: We identification of a novel truncation mutation (p.C108*) in Chromosome 6 Open Reading Frame 25 (C6orf25) gene in this family...
October 15, 2016: European Journal of Haematology
Konrad Pazdrak, Christof Straub, Rosario Maroto, Susan Stafford, Wendy I White, William J Calhoun, Alexander Kurosky
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Leon A Sokulsky, Adam M Collison, Scott Nightingale, Anna Le Fevre, Elizabeth Percival, Malcolm R Starkey, Philip M Hansbro, Paul S Foster, Joerg Mattes
INTRODUCTION: Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNF-related apoptosis-inducing ligand (TRAIL) promotes eosinophilic inflammation through the upregulation of Midline (MID)-1 and subsequent downregulation of Protein Phosphatase 2A (PP2A) but the role of this pathway in EoE that is experimentally induced by repeated food antigen challenges has not been investigated. METHODS: Esophageal mucosal biopsies were collected from children with EoE and controls and assessed for TRAIL and MID-1 protein and mRNA transcript levels...
October 13, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Ting Chen, Juan Xu, Guangquan Liu, Heng Liu, Minjian Chen, Yufeng Qin, Wei Wu, Yankai Xia, Chenbo Ji, Xirong Guo, Juan Wen, Xinru Wang
Genome-wide association studies (GWASs) showed that two single nucleotide polymorphisms (SNPs) (rs17584499 and rs649891) in the protein tyrosine phosphatase receptor type D (PTPRD) were associated with type 2 diabetes (T2D). We sought to determine the influence of the PTPRD variants on the gestational diabetes mellitus (GDM) risk. In this research, two SNPs in PTPRD reported in T2D GWASs and six PTPRD expression-related SNPs were genotyped in 964 GDM cases and 1,021 controls using the Sequenom platform. Logistic regression analyses in additive models showed consistently significant associations of PTPRD rs10511544 A>C, rs10756026 T>A and rs10809070 C>G with a decreased risk of GDM [adjusted OR (95% CI) = 0...
October 12, 2016: Oncotarget
Anastasia Mylona, Francois-Xavier Theillet, Charles Foster, Tammy M Cheng, Francesc Miralles, Paul A Bates, Philipp Selenko, Richard Treisman
Multisite phosphorylation regulates many transcription factors, including the serum response factor partner Elk-1. Phosphorylation of the transcriptional activation domain (TAD) of Elk-1 by the protein kinase ERK at multiple sites potentiates recruitment of the Mediator transcriptional coactivator complex and transcriptional activation, but the roles of individual phosphorylation events had remained unclear. Using time-resolved nuclear magnetic resonance spectroscopy, we found that ERK2 phosphorylation proceeds at markedly different rates at eight TAD sites in vitro, which we classified as fast, intermediate, and slow...
October 14, 2016: Science
Naoko Fujii, Yukinobu Matsuo, Toshiyuki Matsunaga, Satoshi Endo, Hideki Sakai, Masahiko Yamaguchi, Yasuhiro Yamazaki, Junko Sugatani, Akira Ikari
Hypotonic stress decreased claudin-1 and -2 expression levels in renal tubular epithelial HK-2 and Madin-Darby canine kidney cells. Here, we examined the regulatory mechanism involved in this decrease. The hypotonic-induced decrease in claudin expression was inhibited by SB202190, a p38 mitogen-activated protein kinase inhibitor, but not by U0126, a MEK inhibitor, Go6983, a protein kinase C inhibitor, or SP600125, a Jun N-terminal protein kinase inhibitor. Hypotonic stress increased transepithelial electrical resistance, which was inhibited by SB202190...
October 12, 2016: Journal of Biological Chemistry
Cuiyue Wang, Zhen Feng, Kaitong Jiang, Xiuli Zuo
Our goal was to determine the roles and regulatory mechanism of microRNA-935 (miR-935) in the progression of pancreatic cancer. The results showed that, compared with normal pancreatic tissues and cells, the expression of miR-935 was markedly upregulated while INPP4A expression was obviously downregulated in pancreatic cancer tissues and PANC-1 cells. After transfection with miR-935 inhibitor, miR-935 was significantly suppressed, and suppression of miR-935 significantly inhibited cell proliferation, suppressed cell migration, and induced cell apoptosis of pancreatic cancer cells...
October 11, 2016: Oncology Research
Maryam Ataeian, Justus Tegha-Dunghu, Donna G Curtis, Ellen M E Sykes, Ashkan Nozohourmehrabad, Megha Bajaj, Karen Cheung, Martin Srayko
In most animals, female meiosis completes only after fertilization. Sperm entry has been implicated in providing a signal for the initiation of the final meiotic processes, however, a maternal component required for this process has not been previously identified. We report the characterization of a novel family of three highly similar paralogs (memi-1, memi-2, memi-3) that encode oocyte-specific proteins. A hypermorphic mutation memi-1(sb41) results in failure to exit female meiosis II properly, however, loss of all three paralogs results in a "skipped meiosis II" phenotype...
October 11, 2016: Genetics
Jin Young Kim, Garam Kim, Sung-Chul Lim, Hong Seok Choi
LPIN1 is a protein that exhibits dual functions as a phosphatidic acid phosphatase enzyme in regulation of triglyceride and glycerophospholipid metabolism and a transcriptional coregulator. Through unknown tumour-promoting mechanism, LPIN1 frequently observed in various human cancer cell lines controls main cellular processes involved in cancer progression. Here, we demonstrate that LPIN1 enhances the tumour-promoting function of insulin receptor substrate 1 (IRS1) by controlling IRS1 stability. LPIN1 interacts with IRS1 in an insulin growth factor-1-dependent signalling pathway and inhibits its serine phosphorylation, and thereby eliminating ubiquitin-dependent degradation of IRS1 via proteasomal and lysosomal pathways...
October 11, 2016: Carcinogenesis
Sarah Keller, Ryota Inai, Shuhei Sato, Akihiro Tada, Gerhard Adam, Jin Yamamura, Susumu Kanazawa
OBJECTIVE: The radiologic differential diagnosis of giant cell tumors (GCTs) is challenging because there is a risk of misdiagnosis of GCTs as malignant lesions such as atypically presenting osteosarcomas (OSs). This study aims to assess the feasibility of (201)Tl scintigraphy for the differential diagnosis of GCT and atypical OS. MATERIALS AND METHODS: Thallium-201 scintigraphy scans obtained between January 2006 and October 2015 of patients with histologically proven GCT (23 patients [male-to-female ratio, 15:8]; median age, 33...
October 11, 2016: AJR. American Journal of Roentgenology
Sumita Chakrabarti, Andrew Chang, Nai-Jiang Liu, Alan R Gintzler
Caveolin-1 is the predominant structural protein of caveolae, a subset of (lipid) membrane rafts that compartmentalize cell signaling. Caveolin-1 binds most to G protein-coupled receptors and their signaling partners, thereby enhancing interactions among signaling cascade components and the relative activation of specific G protein-coupled pathways. This study reveals that chronic opioid exposure of μ-opioid receptor (MOR) expressing Chinese hamster ovary cells (MOR-CHO) and chronic in vivo morphine exposure of rat spinal cord augmented recruitment of multiple components of MOR-adenylyl cyclase (AC) stimulatory signaling by caveolin-1...
October 10, 2016: Journal of Neurochemistry
Kate A Redgrove, Ilana R Bernstein, Victoria J Pye, Bettina P Mihalas, Jessie M Sutherland, Brett Nixon, Adam McCluskey, Phillip J Robinson, Janet E Holt, Eileen A McLaughlin
The dynamin family of proteins play important regulatory roles in membrane remodelling and endocytosis, especially within brain and neuronal tissues. In the context of reproduction, dynamin 1 (DNM1) and dynamin 2 (DNM2) have recently been shown to act as key mediators of sperm acrosome formation and function. However, little is known about the roles that these proteins play in the developing testicular germ cells. In this study, we employed a DNM2 germ cell-specific knockout model to investigate the role of DNM2 in spermatogenesis...
October 11, 2016: Scientific Reports
Tatiana Jofra, Roberta Di Fonte, Tarun Edgar Hutchinson, Farhad Dastmalchi, Giuseppe Galvani, Manuela Battaglia, Shahram Salek-Ardakani, Georgia Fousteri
PTPN22 (protein tyrosine phosphatase non receptor 22) encodes a tyrosine phosphatase that functions as a key regulator of immune homeostasis. In particular, PTPN22 inhibits T-cell receptor signaling and selectively promotes type I interferon responses in myeloid cells. To date, there is little information on the CD8 T-cell-intrinsic role of PTPN22 in response to a viral pathogen. We unexpectedly found that PTPN22-deficient virus-specific CD8 T cells failed to accumulate in wild-type hosts after lymphocytic choriomeningitis virus infection...
October 11, 2016: Immunology and Cell Biology
Juthika Kundu, In Gyeong Chae, Kyung-Soo Chun
BACKGROUND: Fraxetin (7,8-dihydroxy-6-methoxy coumarin), a coumarin derivative, has been reported to possess antioxidative, anti-inflammatory and neuroprotective effects. A number of recent observations suggest that the induction of heme oxygenase-1 (HO-1) inhibits inflammation and tumorigenesis. In the present study, we determined the effect of fraxetin on HO-1 expression in HaCaT human keratinocytes and investigated its underlying molecular mechanisms. METHODS: Reverse transcriptase-PCR and Western blot analysis were performed to detect HO-1 mRNA and protein expression, respectively...
September 2016: Journal of Cancer Prevention
David L Ebenezer, Panfeng Fu, Vidyani Suryadevara, Yutong Zhao, Viswanathan Natarajan
Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes...
September 29, 2016: Advances in Biological Regulation
Sen Li, Sai-Jie Zuo, Lei Cao, Dong-Zheng Liu, San-Qi Zhang, Yong-Xiao Cao
A novel 3-benzylquinazolin-4(3H)-one derivative Z32, namely 6,7-dimethoxy-3-(3-chloro-4-(4-fluorobenzyloxy)benzyl)quinazolin-4(3H)-one was synthesized. The vasorelaxant and antihypertensive effects of Z32 and its underlying mechanisms were investigated. The following methods were used. The isometric tension of artery ring segments was recorded using an in vitro myography system. Changes in the calcium influx in mesenteric arteries were surveyed using a real-time confocal microscopy. The arterial pressure of spontaneously hypertensive rats was measured in vivo using a non-invasive tail cuff blood pressure system...
October 5, 2016: European Journal of Pharmacology
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