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https://www.readbyqxmd.com/read/29714078/overexpression-of-p21-activated-kinase-2-is-correlated-with-high-grade-oral-squamous-cell-carcinomas
#1
Yao Xiao, Wei-Wei Deng, Lei-Lei Yang, Hao Li, Guang-Tao Yu, Wen-Feng Zhang, Zhi-Jun Sun
AIM: p21-activated kinase 2 (PAK2) is overexpressed in several tumors but the expression of PAK2 in oral squamous cell carcinomas (OSCCs) remains unclear. MATERIALS & METHODS: Immunohistochemistry was performed on human tissue microarrays containing 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa. RESULTS: PAK2 expression was increased in primary OSCC compared with normal mucosa and significantly increased in primary OSCC grade III compared with grade I, but independent of overall survival rate...
May 1, 2018: Future Oncology
https://www.readbyqxmd.com/read/29695509/myc-phosphorylation-in-its-basic-helix-loop-helix-region-destabilizes-transient-%C3%AE-helical-structures-disrupting-max-and-dna-binding
#2
Pavel Macek, Matthew J Cliff, Kevin J Embrey, Geoffrey A Holdgate, J Willem M Nissink, Stanislava Panova, Jonathan P Waltho, Rick A Davies
Myelocytomatosis proto-oncogene transcription factor (Myc) is an intrinsically disordered protein with critical roles in cellular homeostasis and neoplastic transformation. It is tightly regulated in the cell, with Myc phosphorylation playing a major role. In addition to the well-described tandem phosphorylation of Thr-52 and Ser-62 in the Myc transactivation domain linked to its degradation, P21 (RAC1)-activated kinase 2 (PAK2)-mediated phosphorylation of serine and threonine residues in the C-terminal basic helix-loop-helix leucine zip- per (bHLH-LZ) region regulates Myc transcriptional activity...
April 25, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29672153/p21-activated-kinase4-in-pancreatic-acini-is-activated-by-gi-hormones-growth-factors-by-novel-signaling-and-is-needed-to-stimulate-secretory-growth-cascades
#3
Irene Ramos-Alvarez, Robert T Jensen
p21-activated kinases(PAKs) are highly conserved serine/threonine protein kinases, which are divided into two groups:Group-I(PAKs1-3) and Group-II(PAKs4-6). In various tissues, Group-II PAKs play important roles in cytoskeletal dynamics, cell growth as well as neoplastic development/progression. However, little is known about Group-II PAKs role in a number of physiological events including their ability to be activated by gastrointestinal(GI) hormones/neurotransmitters/growth-factors(GFs). We used rat pancreatic acini to explore the ability of GI-hormones/neurotransmitters/GFs to activate Group-II-PAKs and the signaling cascades involved...
April 19, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29661501/mechanical-strain-induced-phospho-proteomic-signaling-in-uterine-smooth-muscle-cells
#4
Christian Copley Salem, Craig Ulrich, David Quilici, Karen Schlauch, Iain L O Buxton, Heather Burkin
Mechanical strain associated with the expanding uterus correlates with increased preterm birth rates. Mechanical signals result in a cascading network of protein phosphorylation events. These signals direct cellular activities and may lead to changes in contractile phenotype and calcium signaling. In this study, the complete phospho-proteome of uterine smooth muscle cells subjected to mechanical strain for 5 min was compared to un-strained controls. Statistically significant, differential phosphorylation events were annotated by Ingenuity Pathway Analysis to elucidate mechanically induced phosphorylation networks...
March 30, 2018: Journal of Biomechanics
https://www.readbyqxmd.com/read/29653269/microrna-26a-is-a-key-regulon-that-inhibits-progression-and-metastasis-of-c-myc-ezh2-double-high-advanced-hepatocellular-carcinoma
#5
Xiang Zhang, Xiao Zhang, Ting Wang, Lei Wang, Zhijun Tan, Wei Wei, Bo Yan, Jing Zhao, Kaichun Wu, Angang Yang, Rui Zhang, Lintao Jia
Overexpressed c-Myc and EZH2 usually mean high malignancy in cancers. Most of mortality from cancer is attributable to metastasis. MicroRNAs(miRNAs), like transcription factors, can regulate hundreds of genes. Here, we identify microRNA-26a (miR-26a) suppresses EZH2 and c-Myc by targeting EZH2 and CDK8 in Wnt pathway. MiR-26a is a well-known tumor-suppressive miRNA in multiple cancers, but how it is downregulated in hepatocellular carcinoma (HCC) is still unclear. Here, we disclose miR-26a is epigenetic silenced by a c-Myc-mediated PRC2-depandent way in HCC...
April 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29510700/an-rnai-screen-of-rho-signalling-networks-identifies-rhoh-as-a-regulator-of-rac1-in-prostate-cancer-cell-migration
#6
Virginia Tajadura-Ortega, Ritu Garg, Richard Allen, Claudia Owczarek, Michael D Bright, Samuel Kean, Aisyah Mohd-Noor, Anita Grigoriadis, Timothy C Elston, Klaus M Hahn, Anne J Ridley
BACKGROUND: Cell migration is essential for development and tissue repair, but it also contributes to disease. Rho GTPases regulate cell migration, but a comprehensive analysis of how each Rho signalling component affects migration has not been carried out. RESULTS: Through an RNA interference screen, and using a prostate cancer cell line, we find that approximately 25% of Rho network components alter migration. Some genes enhance migration while others decrease basal and/or hepatocyte growth factor-stimulated migration...
March 6, 2018: BMC Biology
https://www.readbyqxmd.com/read/29487189/integrated-in-vivo-multiomics-analysis-identifies-p21-activated-kinase-signaling-as-a-driver-of-colitis
#7
Jesse Lyons, Douglas K Brubaker, Phaedra C Ghazi, Katherine R Baldwin, Amanda Edwards, Myriam Boukhali, Samantha Dale Strasser, Lucia Suarez-Lopez, Yi-Jang Lin, Vijay Yajnik, Joseph L Kissil, Wilhelm Haas, Douglas A Lauffenburger, Kevin M Haigis
Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract that has limited treatment options. To gain insight into the pathogenesis of chronic colonic inflammation (colitis), we performed a multiomics analysis that integrated RNA microarray, total protein mass spectrometry (MS), and phosphoprotein MS measurements from a mouse model of the disease. Because we collected all three types of data from individual samples, we tracked information flow from RNA to protein to phosphoprotein and identified signaling molecules that were coordinately or discordantly regulated and pathways that had complex regulation in vivo...
February 27, 2018: Science Signaling
https://www.readbyqxmd.com/read/29455850/proteins-involved-in-the-antioxidant-and-inflammatory-response-in-rutin-treated-human-skin-fibroblasts-exposed-to-uva-or-uvb-irradiation
#8
Agnieszka Gęgotek, Pedro Domingues, Elżbieta Skrzydlewska
BACKGROUND: Rutin, due to its polyphenolic structure, has antioxidant properties and can be used as a cytoprotective compound against UV-induced effects on skin cells. OBJECTIVE: The aim of this study was to examine the effect of rutin on proteomic profile in human skin fibroblasts irradiated with UV dose that induces apoptosis. METHODS: Proteome analysis based on the results obtained by the QExactive OrbiTrap mass spectrometer. RESULTS: Results show that rutin treatment more strongly protects against UVA-induced rather than UVB-induced increases in the total expression of proteins involved in antioxidant (such as SOD, TrxR, and Prxs 1/2) and inflammatory response (e...
June 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29362401/microrna-mir-4779-suppresses-tumor-growth-by-inducing-apoptosis-and-cell-cycle-arrest-through-direct-targeting-of-pak2-and-ccnd3
#9
Kyung Hee Koo, Heechung Kwon
Depending on the function of their target genes, microRNAs (miRNAs) act as either tumor suppressors or oncogenes. Therefore, miRNAs represent a novel therapeutic strategy for prevention and management of cancer by targeting of onco-miRNAs or mimicking of tumor suppressor miRNAs. Herein, we identified novel tumor suppressor miRNAs and investigated their molecular mechanisms. To identify novel tumor suppressor miRNAs, we used 532 human miRNA mimic libraries and measured cell viability using MTS assays. The function of miR-4779 was then analyzed using cell cycle analyses and apoptosis, colony forming, and soft agar assays...
January 23, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29353882/igf1r-signaling-drives-antiestrogen-resistance-through-pak2-pix-activation-in-luminal-breast-cancer
#10
Yinghui Zhang, Lynn Wester, Jichao He, Tamar Geiger, Marja Moerkens, Ram Siddappa, Jean A Helmijr, Mieke M Timmermans, Maxime P Look, Caroline H M van Deurzen, John W M Martens, Chantal Pont, Marjo de Graauw, Erik H J Danen, Els M J J Berns, John H N Meerman, Maurice P H M Jansen, Bob van de Water
Antiestrogen resistance in estrogen receptor positive (ER+ ) breast cancer is associated with increased expression and activity of insulin-like growth factor 1 receptor (IGF1R). Here, a kinome siRNA screen has identified 10 regulators of IGF1R-mediated antiestrogen with clinical significance. These include the tamoxifen resistance suppressors BMPR1B, CDK10, CDK5, EIF2AK1, and MAP2K5, and the tamoxifen resistance inducers CHEK1, PAK2, RPS6KC1, TTK, and TXK. The p21-activated kinase 2, PAK2, is the strongest resistance inducer...
April 2018: Oncogene
https://www.readbyqxmd.com/read/29335522/pyruvate-kinase-m2-promotes-pancreatic-ductal-adenocarcinoma-invasion-and-metastasis-through-phosphorylation-and-stabilization-of-pak2-protein
#11
Tsu-Yao Cheng, Yi-Chieh Yang, Hsiu-Po Wang, Yu-Wen Tien, Chia-Tung Shun, Hsin-Yi Huang, Michael Hsiao, Kuo-Tai Hua
Pyruvate kinase muscle isozymes (PKMs) have crucial roles in regulating metabolic changes during carcinogenesis. A switch from PKM1 to PKM2 isoform was thought to lead to aerobic glycolysis promoting carcinogenesis, and was considered as one of the cancer signatures. However, recent evidence has argued against the existence of PKM isoform switch and related metabolic effects during cancer progression. We compared the effects of PKM1 and PKM2 in cell invasiveness and metastasis of pancreatic ductal adenocarcinoma (PDAC)...
March 2018: Oncogene
https://www.readbyqxmd.com/read/29297928/p21-activated-kinase-2-is-essential-in-maintenance-of-peripheral-foxp3-regulatory-t-cells
#12
Jinyong Choi, David Randall Pease, Siqi Chen, Bin Zhang, Hyewon Phee
The p21-activated kinase 2 (Pak2), an effector molecule of the Rho family GTPases Rac and Cdc42, regulates diverse functions of T cells. Previously, we showed that Pak2 is required for development and maturation of T cells in the thymus, including thymus-derived regulatory T (Treg) cells. However, whether Pak2 is required for the functions of various subsets of peripheral T cells, such as naive CD4 and helper T-cell subsets including Foxp3+ Treg cells, is unknown. To determine the role of Pak2 in CD4 T cells in the periphery, we generated inducible Pak2 knockout (KO) mice, in which Pak2 was deleted in CD4 T cells acutely by administration of tamoxifen...
January 3, 2018: Immunology
https://www.readbyqxmd.com/read/29296839/pak2-regulates-myeloid-derived-suppressor-cell-development-in-mice
#13
Yi Zeng, Seongmin Hahn, Jessica Stokes, Emely A Hoffman, Monika Schmelz, Maria Proytcheva, Jonathan Chernoff, Emmanuel Katsanis
Myeloid-derived suppressor cells (MDSCs) are CD11b+ Gr1+ cells that induce T-cell hyporesponsiveness, thus impairing antitumor immunity. We have previously reported that disruption of Pak2, a member of the p21-activated kinases (Paks), in hematopoietic stem/progenitor cells (HSPCs) induces myeloid lineage skewing and expansion of CD11bhigh Gr1high cells in mice. In this study, we confirmed that Pak2 -KO CD11bhigh Gr1high cells suppressed T-cell proliferation, consistent with an MDSC phenotype. Loss of Pak2 function in HSPCs led to (1) increased hematopoietic progenitor cell sensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, (2) increased MDSC proliferation, (3) decreased MDSC sensitivity to both intrinsic and Fas-Fas ligand-mediated apoptosis, and (4) promotion of MDSCs by Pak2-deficient CD4+ T cells that produced more interferon γ, tumor necrosis factor α, and GM-CSF...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29213081/pak2-is-essential-for-the-function-of-foxp3-regulatory-t-cells-through-maintaining-a-suppressive-treg-phenotype
#14
Kyle L O'Hagan, Stephen D Miller, Hyewon Phee
Foxp3, a key transcription factor that drives lineage differentiation of regulatory T cells (Tregs), was thought to imprint a unique and irreversible genetic signature within Tregs. Recent evidence, however, suggests that loss or attenuation of Foxp3 expression can cause Tregs to de-differentiate into effector T cells capable of producing proinflammatory cytokines. Herein, we report that the signaling kinase, p21-activated kinase 2 (Pak2), is essential for maintaining Treg stability and suppressive function...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29199152/low-level-hg-2-exposure-modulates-the-b-cell-cytoskeletal-phosphoproteome
#15
Nicholas J Carruthers, Allen J Rosenspire, Joseph A Caruso, Paul M Stemmer
Exposure of Wehi-231 B-cells to Hg2+ for 5min resulted in concentration dependent changes in protein phosphorylations. Phosphorylation was quantified using mass spectrometry to analyze TiO2 and anti-pTyr antibody selected phosphopeptides from Wehi-231 digests. The most frequent and largest amplitude responses to Hg2+ exposure were increased phosphorylation although a decrease was observed for 1% of phosphoproteins detected in the untreated cells. A subset of proteins responded with an increase in phosphorylation to Hg2+ exposure at low micromolar concentrations...
February 20, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29124783/a-key-role-for-rac-and-pak-signaling-in-neutrophil-extracellular-traps-nets-formation-defines-a-new-potential-therapeutic-target
#16
Mathilde Gavillet, Kimberly Martinod, Raffaele Renella, Denisa D Wagner, David A Williams
NET formation in mice (NETosis) is supported by reactive oxygen species (ROS) production by NADPH oxidase and histone hypercitrullination by peptidylarginine deiminase 4 (PAD4). Rac1 and Rac2, expressed in polymorphonuclear neutrophils (PMNs), regulate the cytoskeleton, cell shape, adhesion, and migration and are also essential components of the NADPH oxidase complex. We aimed to explore the role of the Rac signaling pathway including the upstream guanosine exchange factor (GEF) activator, Vav, and a downstream effector, the p21-activated kinase, Pak, on NETosis in PMNs using a previously described flow-cytometry-based assay...
February 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29092026/copd-gwas-variant-at-19q13-2-in-relation-with-dna-methylation-and-gene-expression
#17
Ivana Nedeljkovic, Lies Lahousse, Elena Carnero-Montoro, Alen Faiz, Judith M Vonk, Kim de Jong, Diana A van der Plaat, Cleo C van Diemen, Maarten van den Berge, Ma'en Obeidat, Yohan Bossé, David C Nickle, B I O S Consortium, Andre G Uitterlinden, Joyce B J van Meurs, Bruno H C Stricker, Guy G Brusselle, Dirkje S Postma, H Marike Boezen, Cornelia M van Duijn, Najaf Amin
Chronic obstructive pulmonary disease (COPD) is among the major health burdens in adults. While cigarette smoking is the leading risk factor, a growing number of genetic variations have been discovered to influence disease susceptibility. Epigenetic modifications may mediate the response of the genome to smoking and regulate gene expression. Chromosome 19q13.2 region is associated with both smoking and COPD, yet its functional role is unclear. Our study aimed to determine whether rs7937 (RAB4B, EGLN2), a top genetic variant in 19q13...
January 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/28942352/myo18a-an-unusual-myosin
#18
REVIEW
Matthew D Buschman, Seth J Field
MYO18A is a divergent member of the myosin family characterized by the presence of an amino-terminal PDZ domain. MYO18A has been found in a few different complexes involved in intracellular transport processes. MYO18A is found in a complex with LURAP1 and MRCK that functions in retrograde treadmilling of actin. It also has been found in a complex with PAK2, βPIX, and GIT1, functioning to transport that protein complex from focal adhesions to the leading edge. Finally, a high proportion of MYO18A is found in complex with GOLPH3 at the trans Golgi, where it functions to promote vesicle budding for Golgi-to-plasma membrane trafficking...
January 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28789679/consensus-strategy-in-genes-prioritization-and-combined-bioinformatics-analysis-for-preeclampsia-pathogenesis
#19
Eduardo Tejera, Maykel Cruz-Monteagudo, Germán Burgos, María-Eugenia Sánchez, Aminael Sánchez-Rodríguez, Yunierkis Pérez-Castillo, Fernanda Borges, Maria Natália Dias Soeiro Cordeiro, César Paz-Y-Miño, Irene Rebelo
BACKGROUND: Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis...
August 8, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28765936/human-cytomegalovirus-mir-us4-5p-promotes-apoptosis-via-downregulation-of-p21-activated-kinase-2-in-cultured-cells
#20
Yaozhong Shao, Ying Qi, Yujing Huang, Zhongyang Liu, Yanping Ma, Xin Guo, Shujuan Jiang, Zhengrong Sun, Qiang Ruan
The human cytomegalovirus (HCMV) encodes ≥26 microRNAs (miRNAs). These miRNAs are utilized by HCMV to regulate its own genes in addition to the genes of the host cell, during infection. The present study first identified p21‑activated kinase 2 (PAK2) as a target of hcmv‑miR‑US4‑5p, via hybrid polymerase chain reaction, which was further verified using a luciferase reporter assay. The protein expression level of PAK2, detected via western blotting, was demonstrated to be directly downregulated by overexpression of hcmv‑miR‑US4‑5p in HEK293, HELF and THP‑1 cells...
October 2017: Molecular Medicine Reports
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