Kinome Expression Profiling to Target New Therapeutic Avenues in Multiple Myeloma
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Gene Symbol Gene Description ACVR1B Activin a Receptor, Type IB
Table S1. Kinase clones included in human kinase cDNA library for yeast two-hybrid screening Gene Symbol Gene Description ACVR1B activin A receptor, type IB ADCK2 aarF domain containing kinase 2 ADCK4 aarF domain containing kinase 4 AGK multiple substrate lipid kinase;MULK AK1 adenylate kinase 1 AK3 adenylate kinase 3 like 1 AK3L1 adenylate kinase 3 ALDH18A1 aldehyde dehydrogenase 18 family, member A1;ALDH18A1 ALK anaplastic lymphoma kinase (Ki-1) ALPK1 alpha-kinase 1 ALPK2 alpha-kinase 2 AMHR2 anti-Mullerian hormone receptor, type II ARAF v-raf murine sarcoma 3611 viral oncogene homolog 1 ARSG arylsulfatase G;ARSG AURKB aurora kinase B AURKC aurora kinase C BCKDK branched chain alpha-ketoacid dehydrogenase kinase BMPR1A bone morphogenetic protein receptor, type IA BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) BRAF v-raf murine sarcoma viral oncogene homolog B1 BRD3 bromodomain containing 3 BRD4 bromodomain containing 4 BTK Bruton agammaglobulinemia tyrosine kinase BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) C9orf98 chromosome 9 open reading frame 98;C9orf98 CABC1 chaperone, ABC1 activity of bc1 complex like (S. pombe) CALM1 calmodulin 1 (phosphorylase kinase, delta) CALM2 calmodulin 2 (phosphorylase kinase, delta) CALM3 calmodulin 3 (phosphorylase kinase, delta) CAMK1 calcium/calmodulin-dependent protein kinase I CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha CAMK2B calcium/calmodulin-dependent -
Mir-338-3P Functions As a Tumor Suppressor in Gastric Cancer by Targeting PTP1B
Sun et al. Cell Death and Disease DOI 10.1038/s41419-018-0611-0 Cell Death & Disease ARTICLE Open Access miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B Feng Sun1, Mengchao Yu2,JingYu2, Zhijian Liu1,XinyanZhou2,YanqingLiu2, Xiaolong Ge3,HaidongGao2, Mei Li4, Xiaohong Jiang2,SongLiu1,XiChen2 and Wenxian Guan 1 Abstract Gastric cancer (GC) is one of the most common malignant tumors and peritoneal metastasis is the primary cause for advanced GC’s mortality. Protein-tyrosine phosphatase 1B (PTP1B) functions as an oncogene and involves in carcinogenesis and cancer dissemination. However, the function and regulation of PTP1B in GC remain poorly understood. In this study, we found that PTP1B was upregulated in GC tissues and overexpression of PTP1B in vitro promoted cell migration and prevented apoptosis. Then, we predicted that PTP1B was a target of miR-338-3p and we revealed an inverse correlation between miR-338-3p levels and PTP1B protein levels in GC tissues. Next, we verified that PTP1B was inhibited by miR-338-3p via direct targeting to its 3′-untranslated regions. Moreover, overexpression of miR-338-3p in vitro attenuated GC cell migration and promoted apoptosis, and these effects could be partially reversed by reintroduction of PTP1B. Finally, we established an orthotopic xenograft model and a peritoneal dissemination model of GC to demonstrate that miR-338-3p restrained tumor growth and dissemination in vivo by targeting PTP1B. Taken together, our results highlight that PTP1B is an oncogene and is negatively regulated by miR- 1234567890():,; 1234567890():,; 338-3p in GC, which may provide new insights into novel molecular therapeutic targets for GC. -
Exome Sequencing in Bipolar Disorder Reveals Shared Risk Gene AKAP11 with Schizophrenia
medRxiv preprint doi: https://doi.org/10.1101/2021.03.09.21252930; this version posted March 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Exome sequencing in bipolar disorder reveals shared risk gene AKAP11 with schizophrenia Duncan S Palmer1,2,*, Daniel P Howrigan1,2, Sinéad B Chapman2, Rolf Adolfsson3, Nick Bass4, Douglas Blackwood5, Marco PM Boks6, Chia-Yen Chen7,1,2, Claire Churchhouse1,8,2, Aiden P Corvin9, Nicholas Craddock10, David Curtis11,12, Arianna Di Florio13, Faith Dickerson14, Fernando S Goes15, Xiaoming Jia16, Ian Jones10, Lisa Jones17, Lina Jonsson18,19, Rene S Kahn20, Mikael Landén18,21, Adam Locke22, Andrew McIntosh5, Andrew McQuillin4, Derek W Morris23, Michael C O'Donovan24, Roel A Ophoff 25,26, Michael J Owen24, Nancy Pedersen21, Danielle Posthuma27, Andreas Reif28, Neil Risch29, Catherine Schaefer30, Laura Scott31, Tarjinder Singh1,2, Jordan W Smoller32,33, Matthew Solomonson8, David St. Clair34, Eli A Stahl 35, Annabel Vreeker26, James Walters24, Weiqing Wang35, Nicholas A Watts 8, Robert Yolken36, Peter Zandi15, and Benjamin M Neale1,8,2,*. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.03.09.21252930; this version posted March 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. -
ACVR1 Antibody Cat
ACVR1 Antibody Cat. No.: 4791 Western blot analysis of ACVR1 in A549 cell lysate with ACVR1 antibody at 1 μg/mL in (A) the absence and (B) the presence of blocking peptide. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human, Mouse HOMOLOGY: Predicted species reactivity based on immunogen sequence: Bovine: (100%), Rat: (93%) ACVR1 antibody was raised against a 14 amino acid synthetic peptide near the amino terminus of the human ACVR1. IMMUNOGEN: The immunogen is located within the first 50 amino acids of ACVR1. TESTED APPLICATIONS: ELISA, WB ACVR1 antibody can be used for detection of ACVR1 by Western blot at 1 μg/mL. APPLICATIONS: Antibody validated: Western Blot in human samples. All other applications and species not yet tested. At least four isoforms of ACVR1 are known to exist. This antibody is predicted to have no SPECIFICITY: cross-reactivity to ACVR1B or ACVR1C. POSITIVE CONTROL: 1) Cat. No. 1203 - A549 Cell Lysate Properties October 1, 2021 1 https://www.prosci-inc.com/acvr1-antibody-4791.html PURIFICATION: ACVR1 Antibody is affinity chromatography purified via peptide column. CLONALITY: Polyclonal ISOTYPE: IgG CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: ACVR1 Antibody is supplied in PBS containing 0.02% sodium azide. CONCENTRATION: 1 mg/mL ACVR1 antibody can be stored at 4˚C for three months and -20˚C, stable for up to one STORAGE CONDITIONS: year. As with all antibodies care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: ACVR1 ACVR1 Antibody: FOP, ALK2, SKR1, TSRI, ACTRI, ACVR1A, ACVRLK2, Activin receptor type-1, ALTERNATE NAMES: Activin receptor type I, ACTR-I ACCESSION NO.: NP_001096 PROTEIN GI NO.: 4501895 GENE ID: 90 USER NOTE: Optimal dilutions for each application to be determined by the researcher. -
Nucleotide Sequence and Analysis of the 58.3 to 65.5-Kb Early Region of Bacteriophage T4
Volume 14 Number 21 1986 Nucleic Acids Research Nucleotide sequence and analysis of the 58.3 to 65.5-kb early region of bacteriophage T4 Kristoffer Valerie 13.4, John Stevens', Mark Lynch'5, Earl E.Henderson12 and Jon K.de Riel1 'Fels Research Institute, and 2Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA and 3Department of Biochemistry and Biotechnology, Royal Institute of Technology, S-100 44 Stockholm, Sweden Received 21 July 1986; Revised and Accepted 30 September 1986 ABSTRACT The complete 7.2-kb nucleotide sequence from the 58.3 to 65.5-kb early region of bacteriophage T4 has been determined by Maxam and Gilbert sequencing. Computer analysis revealed at least 20 open reading frames (ORFs) within this sequence. All major ORFs are transcribed from the left strand, suggesting that they are expressed early during infection. Among the ORFs, we have identified the pIIII, II, denV and tk genes. The ORFs are very tightly spaced, even over Lapping in some instances, and when ORF interspacing occurs, promoter-like sequences can be implicated. Several of the sequences preceding the ORFs, in particular those at ipIII, ipII, denV, and orf6l.9, can potentially form stable stem-loop structures. INTRODUCTION Recently, considerable progress has been made studying the bacteriophage T4 genome at the molecular level due to the development of T4 strains with unmod- ified DNA suitable for digestion with restriction endonucleases (1). Many T4 genes have since been cloned, sequenced, and their gene products overproduced in Escherichia coli (for review see ref. 2). A majority of the T4 genes studied so far have been essential and non-essential genes with well-characterized pheno- types. -
Characterization of Pulmonary Arteriovenous Malformations in ACVRL1 Versus ENG Mutation Carriers in Hereditary Hemorrhagic Telangiectasia
© American College of Medical Genetics and Genomics ORIGINAL RESEARCH ARTICLE Characterization of pulmonary arteriovenous malformations in ACVRL1 versus ENG mutation carriers in hereditary hemorrhagic telangiectasia Weiyi Mu, ScM1, Zachary A. Cordner, MD, PhD2, Kevin Yuqi Wang, MD3, Kate Reed, MPH, ScM4, Gina Robinson, RN5, Sally Mitchell, MD5 and Doris Lin, MD, PhD5 Purpose: Pulmonary arteriovenous malformations (pAVMs) are mutation carriers to have pAVMs (P o 0.001) or multiple lesions major contributors to morbidity and mortality in hereditary (P = 0.03), and to undergo procedural intervention (P = 0.02). hemorrhagic telangiectasia (HHT). Mutations in ENG and ACVRL1 Additionally, pAVMs in ENG carriers were more likely to exhibit underlie the vast majority of clinically diagnosed cases. The aims of bilateral lung involvement and growth over time, although this did this study were to characterize and compare the clinical and not reach statistical significance. The HHT severity score was morphologic features of pAVMs between these two genotype significantly higher in ENG than in ACVRL1 (P = 0.02). groups. Conclusion: The propensity and multiplicity of ENG-associated Methods: Sixty-six patients with HHT and affected family pAVMs may contribute to the higher disease severity in this members were included. Genotype, phenotypic data, and imaging genotype, as reflected by the HHT severity score and the frequency were obtained from medical records. Morphologic features of of interventional procedures. pAVMs were analyzed using computed tomography angiography. Genet Med HHT symptoms, pAVM imaging characteristics, frequency of advance online publication 19 October 2017 procedural intervention, and HHT severity scores were compared Key Words: ACVRL1; ENG; genotype-phenotype correlation; between ENG and ACVRL1 genotype groups. -
Gpr161 Anchoring of PKA Consolidates GPCR and Camp Signaling
Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling Verena A. Bachmanna,1, Johanna E. Mayrhofera,1, Ronit Ilouzb, Philipp Tschaiknerc, Philipp Raffeinera, Ruth Röcka, Mathieu Courcellesd,e, Federico Apeltf, Tsan-Wen Lub,g, George S. Baillieh, Pierre Thibaultd,i, Pia Aanstadc, Ulrich Stelzlf,j, Susan S. Taylorb,g,2, and Eduard Stefana,2 aInstitute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, 6020 Innsbruck, Austria; bDepartment of Chemistry and Biochemistry, University of California, San Diego, CA 92093; cInstitute of Molecular Biology, University of Innsbruck, 6020 Innsbruck, Austria; dInstitute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada H3C 3J7; eDépartement de Biochimie, Université de Montréal, Montreal, QC, Canada H3C 3J7; fOtto-Warburg Laboratory, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; gDepartment of Pharmacology, University of California, San Diego, CA 92093; hInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom; iDepartment of Chemistry, Université de Montréal, Montreal, QC, Canada H3C 3J7; and jInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, 8010 Graz, Austria Contributed by Susan S. Taylor, May 24, 2016 (sent for review February 18, 2016; reviewed by John J. G. Tesmer and Mark von Zastrow) Scaffolding proteins organize the information flow from activated G accounts for nanomolar binding affinities to PKA R subunit dimers protein-coupled receptors (GPCRs) to intracellular effector cascades (12, 13). Moreover, additional components of the cAMP signaling both spatially and temporally. By this means, signaling scaffolds, such machinery, such as GPCRs, adenylyl cyclases, and phosphodiester- as A-kinase anchoring proteins (AKAPs), compartmentalize kinase ases, physically interact with AKAPs (1, 5, 11, 14). -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Primate Specific Retrotransposons, Svas, in the Evolution of Networks That Alter Brain Function
Title: Primate specific retrotransposons, SVAs, in the evolution of networks that alter brain function. Olga Vasieva1*, Sultan Cetiner1, Abigail Savage2, Gerald G. Schumann3, Vivien J Bubb2, John P Quinn2*, 1 Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, U.K 2 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK 3 Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, D-63225 Germany *. Corresponding author Olga Vasieva: Institute of Integrative Biology, Department of Comparative genomics, University of Liverpool, Liverpool, L69 7ZB, [email protected] ; Tel: (+44) 151 795 4456; FAX:(+44) 151 795 4406 John Quinn: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK, [email protected]; Tel: (+44) 151 794 5498. Key words: SVA, trans-mobilisation, behaviour, brain, evolution, psychiatric disorders 1 Abstract The hominid-specific non-LTR retrotransposon termed SINE–VNTR–Alu (SVA) is the youngest of the transposable elements in the human genome. The propagation of the most ancient SVA type A took place about 13.5 Myrs ago, and the youngest SVA types appeared in the human genome after the chimpanzee divergence. Functional enrichment analysis of genes associated with SVA insertions demonstrated their strong link to multiple ontological categories attributed to brain function and the disorders. SVA types that expanded their presence in the human genome at different stages of hominoid life history were also associated with progressively evolving behavioural features that indicated a potential impact of SVA propagation on a cognitive ability of a modern human. -
Tumor Promoting Effect of BMP Signaling in Endometrial Cancer
International Journal of Molecular Sciences Article Tumor Promoting Effect of BMP Signaling in Endometrial Cancer Tomohiko Fukuda 1,* , Risa Fukuda 1, Kohei Miyazono 1,2,† and Carl-Henrik Heldin 1,*,† 1 Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Box 582, Uppsala University, SE-751 23 Uppsala, Sweden; [email protected] (R.F.); [email protected] (K.M.) 2 Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan * Correspondence: [email protected] (T.F.); [email protected] (C.-H.H.); Tel.: +46-18-4714738 (T.F.); +46-18-4714738 (C.-H.H.) † These authors contributed equally to this work. Abstract: The effects of bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) family, in endometrial cancer (EC) have yet to be determined. In this study, we analyzed the TCGA and MSK-IMPACT datasets and investigated the effects of BMP2 and of TWSG1, a BMP antagonist, on Ishikawa EC cells. Frequent ACVR1 mutations and high mRNA expressions of BMP ligands and receptors were observed in EC patients of the TCGA and MSK-IMPACT datasets. Ishikawa cells secreted higher amounts of BMP2 compared with ovarian cancer cell lines. Exogenous BMP2 stimulation enhanced EC cell sphere formation via c-KIT induction. BMP2 also induced EMT of EC cells, and promoted migration by induction of SLUG. The BMP receptor kinase inhibitor LDN193189 augmented the growth inhibitory effects of carboplatin. Analyses of mRNAs of several BMP antagonists revealed that TWSG1 mRNA was abundantly expressed in Ishikawa cells. -
Multi-Modal Meta-Analysis of 1494 Hepatocellular Carcinoma Samples Reveals
Author Manuscript Published OnlineFirst on September 21, 2018; DOI: 10.1158/1078-0432.CCR-18-0088 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Multi-modal meta-analysis of 1494 hepatocellular carcinoma samples reveals significant impact of consensus driver genes on phenotypes Kumardeep Chaudhary1, Olivier B Poirion1, Liangqun Lu1,2, Sijia Huang1,2, Travers Ching1,2, Lana X Garmire1,2,3* 1Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA 2Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA 3Current affiliation: Department of Computational Medicine and Bioinformatics, Building 520, 1600 Huron Parkway, Ann Arbor, MI 48109 Short Title: Impact of consensus driver genes in hepatocellular carcinoma * To whom correspondence should be addressed. Lana X. Garmire, Department of Computational Medicine and Bioinformatics Medical School, University of Michigan Building 520, 1600 Huron Parkway Ann Arbor-48109, MI, USA, Phone: +1-(734) 615-5510 Current email address: [email protected] Grant Support: This research was supported by grants K01ES025434 awarded by NIEHS through funds provided by the trans-NIH Big Data to Knowledge (BD2K) initiative (http://datascience.nih.gov/bd2k), P20 COBRE GM103457 awarded by NIH/NIGMS, NICHD R01 HD084633 and NLM R01LM012373 and Hawaii Community Foundation Medical Research Grant 14ADVC-64566 to Lana X Garmire. 1 Downloaded from clincancerres.aacrjournals.org on October 1, 2021. © 2018 American Association for Cancer Research. Author Manuscript Published OnlineFirst on September 21, 2018; DOI: 10.1158/1078-0432.CCR-18-0088 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. -
Saracatinib Is an Efficacious Clinical Candidate for Fibrodysplasia Ossificans Progressiva
RESEARCH ARTICLE Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva Eleanor Williams,1 Jana Bagarova,2 Georgina Kerr,1 Dong-Dong Xia,2 Elsie S. Place,3 Devaveena Dey,2 Yue Shen,2 Geoffrey A. Bocobo,2 Agustin H. Mohedas,2 Xiuli Huang,4 Philip E. Sanderson,4 Arthur Lee,4 Wei Zheng,4 Aris N. Economides,5 James C. Smith,3 Paul B. Yu,2 and Alex N. Bullock1 1Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom. 2Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. 3Developmental Biology Laboratory, Francis Crick Institute, London, United Kingdom. 4National Center for Advancing Translational Sciences, NIH, Bethesda, Maryland, USA. 5Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA. Currently, no effective therapies exist for fibrodysplasia ossificans progressiva (FOP), a rare congenital syndrome in which heterotopic bone is formed in soft tissues owing to dysregulated activity of the bone morphogenetic protein (BMP) receptor kinase ALK2 (also known as ACVR1). From a screen of known biologically active compounds, we identified saracatinib as a potent ALK2 kinase inhibitor. In enzymatic and cell-based assays, saracatinib preferentially inhibited ALK2, compared with other receptors of the BMP/TGF-β signaling pathway, and induced dorsalization in zebrafish embryos consistent with BMP antagonism. We further tested the efficacy of saracatinib using an inducible ACVR1Q207D-transgenic mouse line, which provides a model of heterotopic ossification (HO), as well as an inducible ACVR1R206H-knockin mouse, which serves as a genetically and physiologically faithful FOP model. In both models, saracatinib was well tolerated and potently inhibited the development of HO, even when administered transiently following soft tissue injury.