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Protein phosphatase 2a

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https://www.readbyqxmd.com/read/28720534/tgf-%C3%AE-signaling-regulates-p-akt-levels-via-pp2a-during-diapause-entry-in-the-cotton-bollworm-helicoverpa-armigera
#1
Hai-Yin Li, Tao Wang, Yong-Pan Yang, Shao-Lei Geng, Wei-Hua Xu
Akt, which is a key kinase in the insulin signaling pathway, plays important roles in glucose metabolism, cell proliferation, transcription and cell migration. Our previous studies indicated that low insulin levels and high p-Akt levels are present in diapause-destined individuals. Here, we show that PI3K, which is upstream of Akt, is low in diapause-destined pupal brains but high in p-Akt levels, implying that p-Akt is modified by factors other than the insulin signaling pathway. Protein phosphatase 2A (PP2A), which is a key regulator in the TGF-β signaling pathway, can directly bind to and dephosphorylate Akt...
July 15, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28720530/downregulation-of-protein-phosphatase-2a-by-apolipoprotein-e-implications-for-alzheimer-s-disease
#2
Veena Theendakara, Dale E Bredesen, Rammohan V Rao
The apolipoprotein E ε4 allele is the single most important genetic risk factor associated with Alzheimer's disease (AD). Tau phosphorylation and hyperphosphorylation is an underlying feature of AD and is regulated by specific kinases and phosphatases. Among phosphatases, protein phosphatase 2A (PP2A) is the principal tau dephosphorylating enzyme in the brain. Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2AC and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity...
July 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28711506/sodium-selenate-activated-wnt-%C3%AE-catenin-signaling-and-repressed-amyloid-%C3%AE-formation-in-a-triple-transgenic-mouse-model-of-alzheimer-s-disease
#3
Na Jin, Huazhang Zhu, Xiao Liang, Wei Huang, Qingguo Xie, Peng Xiao, Jiazuan Ni, Qiong Liu
Accumulating evidences show that selenium dietary intake is inversely associated with the mortality of Alzheimer's disease (AD). Sodium selenate has been reported to reduce neurofibrillary tangles (NFT) in the tauopathic mouse models, but its effects on the Wnt/β-catenin signaling pathway and APP processing remain unknown during AD formation. In this paper, triple transgenic AD mice (3×Tg-AD) had been treated with sodium selenate in drinking water for 10month before the detection of hippocampal pathology...
July 12, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28700947/acute-dietary-restriction-acts-via-tor-pp2a-and-myc-signaling-to-boost-innate-immunity-in-drosophila
#4
Jung-Eun Lee, Morsi Rayyan, Allison Liao, Isaac Edery, Scott D Pletcher
Dietary restriction promotes health and longevity across taxa through mechanisms that are largely unknown. Here, we show that acute yeast restriction significantly improves the ability of adult female Drosophila melanogaster to resist pathogenic bacterial infections through an immune pathway involving downregulation of target of rapamycin (TOR) signaling, which stabilizes the transcription factor Myc by increasing the steady-state level of its phosphorylated forms through decreased activity of protein phosphatase 2A...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28700668/conditional-cell-reprogramming-involves-non-canonical-%C3%AE-catenin-activation-and-mtor-mediated-inactivation-of-akt
#5
Frank A Suprynowicz, Christopher M Kamonjoh, Ewa Krawczyk, Seema Agarwal, Anton Wellstein, Fadeke A Agboke, Sujata Choudhury, Xuefeng Liu, Richard Schlegel
The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-267362, converts primary epithelial cells growing in vitro into an undifferentiated adult stem cell-like state that is characterized by long-term proliferation. This cell culture method also maintains the proliferation of adult epithelial stem cells from various tissues. Both primary and adult stem cells retain their tissue-specific differentiation potential upon removal of the culture conditions. Due to the ability to modulate the proliferation and differentiation of the cells, this method is referred to as conditional reprogramming and it is increasingly being used in studies of tumor heterogeneity, personalized medicine and regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28692336/positive-selection-analysis-highlights-key-positions-in-plant-pp2a-regulatory-subunits
#6
Matthew A Booker, Alison DeLong
A versatile hub for cellular control, the eukaryotic protein phosphatase 2A (PP2A) enzyme family is thought to achieve specificity through combinatorial complexity. Phylogenetic analysis has revealed that expansion of PP2A gene families resulted from whole genome duplications followed by non-random gene loss, and selection analysis suggests that retention of B56/PPP2R5 gene family members after genome duplication events was driven by functional diversification. Here we identify the sites at which positive selection is detected in the plant B56 gene family, and discuss the significance of selection at these positions in the context of PP2A holoenzyme structure...
July 10, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28681362/protein-phosphatases-1-and-2a-and-their-naturally-occurring-inhibitors-current-topics-in-smooth-muscle-physiology-and-chemical-biology
#7
REVIEW
Akira Takai, Masumi Eto, Katsuya Hirano, Kosuke Takeya, Toshiyuki Wakimoto, Masaru Watanabe
Protein phosphatases 1 and 2A (PP1 and PP2A) are the most ubiquitous and abundant serine/threonine phosphatases in eukaryotic cells. They play fundamental roles in the regulation of various cellular functions. This review focuses on recent advances in the functional studies of these enzymes in the field of smooth muscle physiology. Many naturally occurring protein phosphatase inhibitors with different relative PP1/PP2A affinities have been discovered and are widely used as powerful research tools. Current topics in the chemical biology of PP1/PP2A inhibitors are introduced and discussed, highlighting the identification of the gene cluster responsible for the biosynthesis of calyculin A in a symbiont microorganism of a marine sponge...
July 5, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28678918/cantharidin-suppressed-breast-cancer-mda-mb-231-cell-growth-and-migration-by-inhibiting-mapk-signaling-pathway
#8
X-D Gu, L-L Xu, H Zhao, J-Z Gu, X-H Xie
As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment...
July 3, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28677734/overexpression-of-set-oncoprotein-is-associated-with-tumor-progression-and-poor-prognosis-in-human-gastric-cancer
#9
Xiaoning Yuan, Te Zhang, Xin Zheng, Yunfei Zhang, Tingting Feng, Pengfei Liu, Zhiting Sun, Shanshan Qin, Xuewen Liu, Liang Zhang, Jie Song, Ying Liu
SE translocation (SET) oncoprotein, an inhibitor of protein phosphatase 2A, is abnormally expressed in many cancers. In this study, SET was aberrantly upregulated in gastric cancer (GC) compared with control tissues. Clinicopathological analysis showed that SET expression was significantly correlated with pathological grade (p=0.002), lymph node stage (p=0.014), and invasive depth (p=0.022). Kaplan-Meier analysis indicated that patients with high SET expression showed poorer overall survival rates than those with low SET expression...
July 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28665315/myc-modulation-around-the-cdk2-p27-skp2-axis
#10
REVIEW
Per Hydbring, Alina Castell, Lars-Gunnar Larsson
MYC is a pleiotropic transcription factor that controls a number of fundamental cellular processes required for the proliferation and survival of normal and malignant cells, including the cell cycle. MYC interacts with several central cell cycle regulators that control the balance between cell cycle progression and temporary or permanent cell cycle arrest (cellular senescence). Among these are the cyclin E/A/cyclin-dependent kinase 2 (CDK2) complexes, the CDK inhibitor p27(KIP1) (p27) and the E3 ubiquitin ligase component S-phase kinase-associated protein 2 (SKP2), which control each other by forming a triangular network...
June 30, 2017: Genes
https://www.readbyqxmd.com/read/28656346/light-regulation-of-nitrate-reductase-by-catalytic-subunits-of-protein-phosphatase-2a
#11
Maria T Creighton, Maite Sanmartín, Amr R A Kataya, Irina O Averkina, Behzad Heidari, Dugassa Nemie-Feyissa, Jose J Sánchez-Serrano, Cathrine Lillo
PP2A catalytic subunit C2 is of special importance for light/dark regulation of nitrate reductase activity. The level of unmethylated PP2A catalytic subunits decreases in darkness. Protein phosphatase 2A (PP2A) dephosphorylates and activates nitrate reductase (NR) in photosynthetically active tissue when plants are transferred from darkness to light. In the present work, investigation of Arabidopsis thaliana PP2A mutant lines revealed that one of the five PP2A catalytic subunit genes, e.g., C2, was of special importance for NR activation...
June 27, 2017: Planta
https://www.readbyqxmd.com/read/28656258/cip2a-an-oncoprotein-is-associated-with-cell-proliferation-invasion-and-migration-in-laryngeal-carcinoma-cells
#12
Xu-Dong Chen, Shi-Xiong Tang, Jian-Hua Zhang, Li-Tao Zhang, Yao-Wen Wang
Laryngeal carcinoma is one of the most common malignant tumors in otorhinolaryngology. Moreover, experimental investigation showed that cancerous inhibitor of protein phosphatase 2A (CIP2A) expressed highly in various cancers. Therefore, we investigated whether CIP2A can regulate the proliferation, invasion and migration by RNA interference in Hep-2 cells and AMC-NH-8 cells and further affect the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Overexpression of CIP2A was evaluated in tumor tissue and laryngeal cancer cell lines (Hep-2 and AMC-NH-8 cells) by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay...
June 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28655918/the-role-of-set-i2pp2a-in-canine-mammary-tumors
#13
Satoru Kake, Shunya Tsuji, Shuhei Enjoji, Sayaka Hanasaki, Hiroshi Hayase, Ryotaro Yabe, Yuiko Tanaka, Takayuki Nakagawa, Hao-Ping Liu, Shih-Chieh Chang, Tatsuya Usui, Takashi Ohama, Koichi Sato
Canine mammary tumor is the most common neoplasm in female dogs, and it has generated considerable attention as a translational model for human breast cancer. Ser/Thr protein phosphatase 2A (PP2A) plays a critical role as a tumor suppressor, and SET/I2PP2A, the endogenous inhibitory protein of PP2A, binds directly to PP2A and suppresses its phosphatase activity. Here, we investigated the role of SET in the tumorigenic growth in canine mammary tumor as well as in the sensitivity of tumors to existing therapeutics...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28652527/hyperglycemia-reduces-pp2a-subunit-b-expression-in-a-middle-cerebral-artery-occlusion-animal-model
#14
Dong-Ju Park, Phil-Ok Koh
Diabetes is a metabolic disorder that worsens clinical outcome following cerebral ischemia. Protein phosphatase 2A (PP2A) is a conserved, heterotrimeric, serine/threonine phosphatase with various cellular functions. PP2A subunit B is abundant in brain tissue and modulates PP2A function. The aim of this study was to investigate PP2A subunit B protein expression in the cerebral cortex of non-diabetic and diabetic animals with middle cerebral artery occlusion (MCAO) injury. Sprague-Dawley rats were injected with streptozotocin (40 mg/kg, i...
June 26, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28634862/effect-of-gapt-extract-on-expression-of-tau-protein-and-its-phosphorylation-related-enzymes-in-hippocampal-neurons-of-appv717i-transgenic-mice
#15
Jing-Nian Ni, Jing Shi, Xue-Kai Zhang, Yi-Chang Yang, Xiao-Meng Liu, Ming-Qing Wei, Ting Li, Peng-Wen Wang, Jin-Zhou Tian, Yong-Yan Wang
OBJECTIVE: To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice. METHODS: Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg d)], the low, medium and high dosage of GAPT groups [0...
June 20, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28613156/reciprocal-regulation-of-arpp-16-by-pka-and-mast3-kinases-provides-a-camp-regulated-switch-in-protein-phosphatase-2a-inhibition
#16
Veronica Musante, Lu Li, Jean Kanyo, Tukiet T Lam, Christopher M Colangelo, Shuk Kei Cheng, A Harrison Brody, Paul Greengard, Nicolas Le Novère, Angus C Nairn
ARPP-16, ARPP-19, and ENSA are inhibitors of protein phosphatase PP2A. ARPP-19 and ENSA phosphorylated by Greatwall kinase inhibit PP2A during mitosis. ARPP-16 is expressed in striatal neurons where basal phosphorylation by MAST3 kinase inhibits PP2A and regulates key components of striatal signaling. The ARPP-16/19 proteins were discovered as substrates for PKA, but the function of PKA phosphorylation is unknown. We find that phosphorylation by PKA or MAST3 mutually suppresses the ability of the other kinase to act on ARPP-16...
June 14, 2017: ELife
https://www.readbyqxmd.com/read/28612433/musculin-inhibits-human-t-helper-17-cell-response-to-interleukin-2-by-controlling-stat5b-activity
#17
Veronica Santarlasci, Alessio Mazzoni, Manuela Capone, Maria Caterina Rossi, Laura Maggi, Gianni Montaini, Beatrice Rossettini, Rolando Cimaz, Matteo Ramazzotti, Giusi Barra, Raffaele De Palma, Enrico Maggi, Francesco Liotta, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
We recently demonstrated that human T-helper (Th) 17 cells, unlike Th1 cells, do not proliferate in response to T-cell receptor stimulation, mainly because of their reduced capacity to produce and respond to IL-2. In this study, we show that their lower responsiveness to IL-2 is due to the selective expression of Musculin (MSC), a member of the basic helix-loop-helix transcription factors. We show that MSC expression in human Th17 cells is retinoic acid orphan receptor (ROR)γt-dependent, and allows the upregulation of PPP2R2B, a regulatory member of the protein phosphatase 2A (PP2A) enzyme...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28603063/overexpression-of-phosphoprotein-phosphatase-2a-predicts-worse-prognosis-in-patients-with-breast-cancer-a-15-year-follow-up
#18
Po-Ming Chen, Pei-Yi Chu, Shiao-Lin Tung, Chun-Yu Liu, Yi-Fang Tsai, Yen-Shu Lin, Wan-Lun Wang, Yu-Ling Wang, Pei-Ju Lien, Ta-Chung Chao, Ling-Ming Tseng
Breast cancer subtypes can be stratified by immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2). The signaling pathways mediated by these receptors are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. One of the most frequently overactivated pathways in breast cancer is the AKT signaling cascade. Protein phosphatase 2A (PP2A) acts as a switch to turn off signal transduction in the AKT pathway; however, it is frequently inactivated in many cancers by phosphorylation of Tyr-307 to form phosphoprotein phosphatase 2A (p-PP2A)...
June 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28587927/the-%C3%AE-4-subunit-of-the-voltage-gated-calcium-channel-cacnb4-regulates-the-rate-of-cell-proliferation-in-chinese-hamster-ovary-cells
#19
Mohamad Rima, Marwa Daghsni, Stephan De Waard, Nathalie Gaborit, Ziad Fajloun, Michel Ronjat, Yasuo Mori, Juan L Brusés, Michel De Waard
The β subunits of Voltage-Gated Calcium Channel (VGCC) are cytosolic proteins that interact with the VGCC pore -forming subunit and participate in the trafficking of the channel to the cell membrane and in ion influx regulation. β subunits also exert functions independently of their binding to VGCC by translocation to the cell nucleus including the control of gene expression. Mutations of the neuronal Cacnb4 (β4) subunit are linked to human neuropsychiatric disorders including epilepsy and intellectual disabilities...
June 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28586756/inhibitors-of-the-pi3k-mtor-pathway-prevent-stat5-phosphorylation-in-jak2v617f-mutated-cells-through-pp2a-cip2a-axis
#20
Niccolò Bartalucci, Laura Calabresi, Manjola Balliu, Serena Martinelli, Maria Caterina Rossi, Jean Luc Villeval, Francesco Annunziato, Paola Guglielmelli, Alessandro M Vannucchi
Inhibition of the constitutively activated JAK/STAT pathway in JAK2V617F mutated cells by the JAK1/JAK2 inhibitor ruxolitinib resulted in clinical benefits in patients with myeloproliferative neoplasms. However, evidence of disease-modifying effects remains scanty; furthermore, some patients do not respond adequately to ruxolitinib, or have transient responses, thus novel treatment strategies are needed. Here we demonstrate that ruxolitinib causes incomplete inhibition of STAT5 in JAK2V617F mutated cells due to persistence of phosphorylated serine residues of STAT5b, that conversely are targeted by PI3K and mTORC1 inhibitors...
May 22, 2017: Oncotarget
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