Frequent Alterations in the Expression of Serine/Threonine Kinases In
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The Role of LIM Kinase 1 and Its Substrates in Cell Cycle Progression
University of Central Florida STARS Electronic Theses and Dissertations, 2004-2019 2014 The Role of LIM Kinase 1 and its Substrates in Cell Cycle Progression Lisa Ritchey University of Central Florida Part of the Medical Sciences Commons Find similar works at: https://stars.library.ucf.edu/etd University of Central Florida Libraries http://library.ucf.edu This Doctoral Dissertation (Open Access) is brought to you for free and open access by STARS. It has been accepted for inclusion in Electronic Theses and Dissertations, 2004-2019 by an authorized administrator of STARS. For more information, please contact [email protected]. STARS Citation Ritchey, Lisa, "The Role of LIM Kinase 1 and its Substrates in Cell Cycle Progression" (2014). Electronic Theses and Dissertations, 2004-2019. 1300. https://stars.library.ucf.edu/etd/1300 THE ROLE OF LIM KINASE 1 AND ITS SUBSTRATES IN CELL CYCLE PROGRESSION by LISA RITCHEY B.S. Florida State University 2007 M.S. University of Central Florida 2010 A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Burnett School of Biomedical Sciences in the College of Graduate Studies at the University of Central Florida Orlando, Florida Summer Term 2014 Major Professor: Ratna Chakrabarti © 2014 Lisa Ritchey ii ABSTRACT LIM Kinase 1 (LIMK1), a modulator of actin and microtubule dynamics, has been shown to be involved in cell cycle progression. In this study we examine the role of LIMK1 in G1 phase and mitosis. We found ectopic expression of LIMK1 resulted in altered expression of p27Kip1, the G1 phase Cyclin D1/Cdk4 inhibitor. -
The Role of P21-Activated Protein Kinase 1 in Metabolic Homeostasis
THE ROLE OF P21-ACTIVATED PROTEIN KINASE 1 IN METABOLIC HOMEOSTASIS by YU-TING CHIANG A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Physiology University of Toronto © Copyright by Yu-ting Chiang 2014 The Role of P21-Activated Protein Kinase 1 in Metabolic Homeostasis Yu-ting Chiang Doctor of Philosophy Department of Physiology University of Toronto 2014 Abstract Our laboratory has demonstrated previously that the proglucagon gene (gcg), which encodes the incretin hormone GLP-1, is among the downstream targets of the Wnt signaling pathway; and that Pak1 mediates the stimulatory effect of insulin on Wnt target gene expression in mouse gut non- endocrine cells. Here, I asked whether Pak1 controls gut gcg expression and GLP-1 production, and whether Pak1 deletion leads to impaired metabolic homeostasis in mice. I detected the expression of Pak1 and two other group I Paks in the gut endocrine L cell line GLUTag, and co- localized Pak1 and GLP-1 in the mouse gut. Insulin was shown to stimulate Pak1 Thr423 and β-cat Ser675 phosphorylation. The stimulation of insulin on β-cat Ser675 phosphorylation, gcg promoter activity and gcg mRNA expression could be attenuated by the Pak inhibitor IPA3. Male Pak1-/- mice showed significant reduction in both gut and brain gcg expression levels, and attenuated elevation of plasma GLP-1 levels in response to oral glucose challenge. Notably, the Pak1-/- mice were intolerant to both intraperitoneal and oral glucose administration. Aged Pak1-/- mice showed a severe defect in response to intraperitoneal pyruvate challenge (IPPTT). -
ALS2CR2 (STRADB) 406-418) Goat Polyclonal Antibody – AP08962PU-N
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for AP08962PU-N ALS2CR2 (STRADB) 406-418) Goat Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: ELISA, IHC, WB Recommended Dilution: ELISA: 1/32000. Immunohistochemistry on Paraffin Sections: 3.75 µg/ml. Western Blot: 1 - 3 µg/ml. Reactivity: Canine, Human Host: Goat Clonality: Polyclonal Immunogen: Synthetic peptide from C-terminus of human ALS2CR2 Specificity: This antibody reacts to STE20-Related Kinase Adaptor Beta (STRADB/ALS2CR2) at aa 406-418. It is expected to recognise both human isoforms: ILPIP-alpha (NP_061041.2) and ILPIP-beta (AAF71042.1). Formulation: Tris saline buffer, pH 7.3, 0.5% BSA, 0.02% sodium azide State: Aff - Purified State: Liquid purified Ig Concentration: lot specific Purification: Immunoaffinity Chromatography Conjugation: Unconjugated Storage: Store the antibody undiluted at 2-8°C for one month or (in aliquots) at -20°C for longer. Avoid repeated freezing and thawing. Stability: Shelf life: one year from despatch. Database Link: Entrez Gene 55437 Human Q9C0K7 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 3 ALS2CR2 (STRADB) 406-418) Goat Polyclonal Antibody – AP08962PU-N Background: Amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2, is connected to transferase/kinase activity and ATP binding, it has recently been shown to interact with XIAP, a member of the IAP (Inhibitor of Apoptosis) protein family. -
Evidence for Differential Alternative Splicing in Blood of Young Boys With
Stamova et al. Molecular Autism 2013, 4:30 http://www.molecularautism.com/content/4/1/30 RESEARCH Open Access Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders Boryana S Stamova1,2,5*, Yingfang Tian1,2,4, Christine W Nordahl1,3, Mark D Shen1,3, Sally Rogers1,3, David G Amaral1,3 and Frank R Sharp1,2 Abstract Background: Since RNA expression differences have been reported in autism spectrum disorder (ASD) for blood and brain, and differential alternative splicing (DAS) has been reported in ASD brains, we determined if there was DAS in blood mRNA of ASD subjects compared to typically developing (TD) controls, as well as in ASD subgroups related to cerebral volume. Methods: RNA from blood was processed on whole genome exon arrays for 2-4–year-old ASD and TD boys. An ANCOVA with age and batch as covariates was used to predict DAS for ALL ASD (n=30), ASD with normal total cerebral volumes (NTCV), and ASD with large total cerebral volumes (LTCV) compared to TD controls (n=20). Results: A total of 53 genes were predicted to have DAS for ALL ASD versus TD, 169 genes for ASD_NTCV versus TD, 1 gene for ASD_LTCV versus TD, and 27 genes for ASD_LTCV versus ASD_NTCV. These differences were significant at P <0.05 after false discovery rate corrections for multiple comparisons (FDR <5% false positives). A number of the genes predicted to have DAS in ASD are known to regulate DAS (SFPQ, SRPK1, SRSF11, SRSF2IP, FUS, LSM14A). In addition, a number of genes with predicted DAS are involved in pathways implicated in previous ASD studies, such as ROS monocyte/macrophage, Natural Killer Cell, mTOR, and NGF signaling. -
PINK1, Parkin, and DJ-1 Mutations in Italian Patients with Early-Onset Parkinsonism
European Journal of Human Genetics (2005) 13, 1086–1093 & 2005 Nature Publishing Group All rights reserved 1018-4813/05 $30.00 www.nature.com/ejhg ARTICLE PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism Christine Klein*,1,2,9, Ana Djarmati1,2,3,9, Katja Hedrich1,2, Nora Scha¨fer1,2, Cesa Scaglione4, Roberta Marchese5, Norman Kock1,2, Birgitt Schu¨le1,2, Anja Hiller1, Thora Lohnau1,2, Susen Winkler1,2, Karin Wiegers1,2, Robert Hering6, Peter Bauer6, Olaf Riess6, Giovanni Abbruzzese5, Paolo Martinelli4 and Peter P Pramstaller7,8 1Department of Neurology, University of Lu¨beck, Lu¨beck, Germany; 2Department of Human Genetics, University of Lu¨beck, Lu¨beck, Germany; 3Faculty of Biology, University of Belgrade, Belgrade, Serbia; 4Institute of Neurology, University of Bologna, Bologna, Italy; 5Department of Neurology, University of Genova, Genova, Italy; 6Department of Medical Genetics, University of Tu¨bingen, Tu¨bingen, Germany; 7Department of Neurology, General Regional Hospital, Bolzano-Bozen, Italy; 8Department of Genetic Medicine, EURAC-Research, Bolzano-Bozen, Italy Recessively inherited early-onset parkinsonism (EOP) has been associated with mutations in the Parkin, DJ-1, and PINK1 genes. We studied the prevalence of mutations in all three genes in 65 Italian patients (mean age of onset: 43.275.4 years, 62 sporadic, three familial), selected by age at onset equal or younger than 51 years. Clinical features were compatible with idiopathic Parkinson’s disease in all cases. To detect small sequence alterations in Parkin, DJ-1, and PINK1, we performed a conventional mutational analysis (SSCP/ dHPLC/sequencing) of all coding exons of these genes. -
Kinome Profiling of Clinical Cancer Specimens
Published OnlineFirst March 23, 2010; DOI: 10.1158/0008-5472.CAN-09-3989 Review Cancer Research Kinome Profiling of Clinical Cancer Specimens Kaushal Parikh and Maikel P. Peppelenbosch Abstract Over the past years novel technologies have emerged to enable the determination of the transcriptome and proteome of clinical samples. These data sets will prove to be of significant value to our elucidation of the mechanisms that govern pathophysiology and may provide biological markers for future guidance in person- alized medicine. However, an equally important goal is to define those proteins that participate in signaling pathways during the disease manifestation itself or those pathways that are made active during successful clinical treatment of the disease: the main challenge now is the generation of large-scale data sets that will allow us to define kinome profiles with predictive properties on the outcome-of-disease and to obtain insight into tissue-specific analysis of kinase activity. This review describes the current techniques available to gen- erate kinome profiles of clinical tissue samples and discusses the future strategies necessary to achieve new insights into disease mechanisms and treatment targets. Cancer Res; 70(7); 2575–8. ©2010 AACR. Background the current state of the cell or tissue as characterized by pro- teomic and metabolic measurements (3). The past five years have seen an exponential increase in In this review we describe and evaluate the various tech- technological development to explore the genome and the niques that have recently become available to study the ki- proteome to understand the molecular basis of disease. How- nomes of clinical tissue samples. -
Protein Kinases Phosphorylation/Dephosphorylation Protein Phosphorylation Is One of the Most Important Mechanisms of Cellular Re
Protein Kinases Phosphorylation/dephosphorylation Protein phosphorylation is one of the most important mechanisms of cellular responses to growth, stress metabolic and hormonal environmental changes. Most mammalian protein kinases have highly a homologous 30 to 32 kDa catalytic domain. • Most common method of reversible modification - activation and localization • Up to 1/3 of cellular proteins can be phosphorylated • Leads to a very fast response to cellular stress, hormonal changes, learning processes, transcription regulation .... • Different than allosteric or Michealis Menten regulation Protein Kinome To date – 518 human kinases known • 50 kinase families between yeast, invertebrate and mammaliane kinomes • 518 human PKs, most (478) belong to single super family whose catalytic domain are homologous. • Kinase dendrogram displays relative similarities based on catalytic domains. • AGC (PKA, PKG, PKC) • CAMK (Casein kinase 1) • CMGC (CDC, MAPK, GSK3, CLK) • STE (Sterile 7, 11 & 20 kinases) • TK (Tryosine kinases memb and cyto) • TKL (Tyrosine kinase-like) • Phosphorylation stabilized thermodynamically - only half available energy used in adding phosphoryl to protein - change in free energy forces phosphorylation reaction in one direction • Phosphatases reverse direction • The rate of reaction of most phosphatases are 1000 times faster • Phosphorylation occurs on Ser/The or Tyr • What differences occur due to the addition of a phosphoryl group? • Regulation of protein phosphorylation varies depending on protein - some turned on or off -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Anti-CLK2 Antibody (ARG66787)
Product datasheet [email protected] ARG66787 Package: 100 μg anti-CLK2 antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes CLK2 Tested Reactivity Hu Tested Application IHC-P, WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name CLK2 Antigen Species Human Immunogen Synthetic peptide between aa. 1-50 of Human CLK2. Conjugation Un-conjugated Alternate Names CDC-like kinase 2; Dual specificity protein kinase CLK2; EC 2.7.12.1 Application Instructions Application table Application Dilution IHC-P 1:100 - 1:300 WB 1:500 - 1:2000 Application Note * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Positive Control COLO205 and A549 Calculated Mw 60 kDa Observed Size ~ 60 kDa Properties Form Liquid Purification Affinity purification with immunogen. Buffer PBS, 0.02% Sodium azide, 50% Glycerol and 0.5% BSA. Preservative 0.02% Sodium azide Stabilizer 50% Glycerol and 0.5% BSA Concentration 1 mg/ml Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. www.arigobio.com 1/3 Note For laboratory research only, not for drug, diagnostic or other use. Bioinformation Gene Symbol CLK2 Gene Full Name CDC-like kinase 2 Background This gene encodes a dual specificity protein kinase that phosphorylates serine/threonine and tyrosine- containing substrates. -
Dissecting the Regulatory Activity and Sequence Content of Loci with Exceptional Numbers of Transcription Factor Associations
Downloaded from genome.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Research Dissecting the regulatory activity and sequence content of loci with exceptional numbers of transcription factor associations Ryne C. Ramaker,1,2,4 Andrew A. Hardigan,1,2,4 Say-Tar Goh,3 E. Christopher Partridge,1 Barbara Wold,3 Sara J. Cooper,1 and Richard M. Myers1 1HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA; 2Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA; 3California Institute of Technology, Division of Biology and Biological Engineering, Pasadena, California 91125, USA DNA-associated proteins (DAPs) classically regulate gene expression by binding to regulatory loci such as enhancers or pro- moters. As expanding catalogs of genome-wide DAP binding maps reveal thousands of loci that, unlike the majority of con- ventional enhancers and promoters, associate with dozens of different DAPs with apparently little regard for motif preference, an understanding of DAP association and coordination at such regulatory loci is essential to deciphering how these regions contribute to normal development and disease. In this study, we aggregated publicly available ChIP- seq data from 469 human DAPs assayed in three cell lines and integrated these data with an orthogonal data set of 352 non- redundant, in vitro–derived motifs mapped to the genome within DNase I hypersensitivity footprints to characterize re- gions with high numbers of DAP associations. We establish a generalizable definition for high occupancy target (HOT) loci and identify putative driver DAP motifs in HepG2 cells, including HNF4A, SP1, SP5, and ETV4, that are highly prevalent and show sequence conservation at HOT loci. -
Dissertation
Regulation of gene silencing: From microRNA biogenesis to post-translational modifications of TNRC6 complexes DISSERTATION zur Erlangung des DOKTORGRADES DER NATURWISSENSCHAFTEN (Dr. rer. nat.) der Fakultät Biologie und Vorklinische Medizin der Universität Regensburg vorgelegt von Johannes Danner aus Eggenfelden im Jahr 2017 Das Promotionsgesuch wurde eingereicht am: 12.09.2017 Die Arbeit wurde angeleitet von: Prof. Dr. Gunter Meister Johannes Danner Summary ‘From microRNA biogenesis to post-translational modifications of TNRC6 complexes’ summarizes the two main projects, beginning with the influence of specific RNA binding proteins on miRNA biogenesis processes. The fate of the mature miRNA is determined by the incorporation into Argonaute proteins followed by a complex formation with TNRC6 proteins as core molecules of gene silencing complexes. miRNAs are transcribed as stem-loop structured primary transcripts (pri-miRNA) by Pol II. The further nuclear processing is carried out by the microprocessor complex containing the RNase III enzyme Drosha, which cleaves the pri-miRNA to precursor-miRNA (pre-miRNA). After Exportin-5 mediated transport of the pre-miRNA to the cytoplasm, the RNase III enzyme Dicer cleaves off the terminal loop resulting in a 21-24 nt long double-stranded RNA. One of the strands is incorporated in the RNA-induced silencing complex (RISC), where it directly interacts with a member of the Argonaute protein family. The miRNA guides the mature RISC complex to partially complementary target sites on mRNAs leading to gene silencing. During this process TNRC6 proteins interact with Argonaute and recruit additional factors to mediate translational repression and target mRNA destabilization through deadenylation and decapping leading to mRNA decay. -
Isolation of Cdnas from the Cri-Du-Chat Critical Region by Direct Screening of a Chromosome 5-Specific Cdna Library Andrew D
Downloaded from genome.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH Isolation of cDNAs from the Cri-du-chat Critical Region by Direct Screening of a Chromosome 5-Specific cDNA Library Andrew D. Simmons, 1 Joan Overhauser, 2 and Michael Lovett 1'3 1Departments of Otorhinolaryngology, Molecular Biology and Oncology, and The McDermott Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235; 2Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 Chromosome-specific cDNA libraries are new tools for the isolation of genes from specific genomic regions. We have used two YACs than span the -2-Mb cri-du-chat critical region (CDCCR} of chromosome 5p to directly screen a chromosome 5-specific (CHSSP} fetal brain cDNA library. To compare this library with other sources for new gene discovery, the YACs were hybridized to a normalized infant brain (NIB} cDNA library that has been used extensively for expressed sequence tag (EST} generation. These screens yielded 12 cDNAs from the CH5SP fetal brain library and four cDNAs from the NIB library that mapped to discrete intervals within the CDCCR. Four cDNAs mapped within the minimal CDCCR deletion interval, with the remaining cDNAs being located beyond the boundaries. Only one cDNA shared sequence overlap between the CH5SP and NIB sets of clones. None of the remaining II CHSSP cDNAs were homologous to EST sequences, suggesting, in common with previous data on these libraries, that chromosome-specific cDNA libraries are a rich source of new expressed sequences. The single cDNA that did overlap with the NIB library contained two copies of a sequence motif shared with thrombospondin, properdin, and several complement proteins.