1. Characterisation of Compounds 2, 7, 12, 13, 15-20 2. Labbook Codes and SMILES for 2, 7, 15-17, 20 3
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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 -
Reframing Psychiatry for Precision Medicine
Reframing Psychiatry for Precision Medicine Elizabeth B Torres 1,2,3* 1 Rutgers University Department of Psychology; [email protected] 2 Rutgers University Center for Cognitive Science (RUCCS) 3 Rutgers University Computer Science, Center for Biomedicine Imaging and Modelling (CBIM) * Correspondence: [email protected]; Tel.: (011) +858-445-8909 (E.B.T) Supplementary Material Sample Psychological criteria that sidelines sensory motor issues in autism: The ADOS-2 manual [1, 2], under the “Guidelines for Selecting a Module” section states (emphasis added): “Note that the ADOS-2 was developed for and standardized using populations of children and adults without significant sensory and motor impairments. Standardized use of any ADOS-2 module presumes that the individual can walk independently and is free of visual or hearing impairments that could potentially interfere with use of the materials or participation in specific tasks.” Sample Psychiatric criteria from the DSM-5 [3] that does not include sensory-motor issues: A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history (examples are illustrative, not exhaustive, see text): 1. Deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions. 2. Deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication. -
Systematic Screening for Potential Therapeutic Targets in Osteosarcoma Through a Kinome-Wide CRISPR-Cas9 Library
Cancer Biol Med 2020. doi: 10.20892/j.issn.2095-3941.2020.0162 ORIGINAL ARTICLE Systematic screening for potential therapeutic targets in osteosarcoma through a kinome-wide CRISPR-Cas9 library Yuanzhong Wu*, Liwen Zhou*, Zifeng Wang, Xin Wang, Ruhua Zhang, Lisi Zheng, Tiebang Kang Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China ABSTRACT Objective: Osteosarcoma is the most common primary malignant bone tumor. However, the survival of patients with osteosarcoma has remained unchanged during the past 30 years, owing to a lack of efficient therapeutic targets. Methods: We constructed a kinome-targeting CRISPR-Cas9 library containing 507 kinases and 100 nontargeting controls and screened the potential kinase targets in osteosarcoma. The CRISPR screening sequencing data were analyzed with the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) Python package. The functional data were applied in the 143B cell line through lenti-CRISPR-mediated gene knockout. The clinical significance of kinases in the survival of patients with osteosarcoma was analyzed in the R2: Genomics Analysis and Visualization Platform. Results: We identified 53 potential kinase targets in osteosarcoma. Among these targets, we analyzed 3 kinases, TRRAP, PKMYT1, and TP53RK, to validate their oncogenic functions in osteosarcoma. PKMYT1 and TP53RK showed higher expression in osteosarcoma than in normal bone tissue, whereas TRRAP showed no significant difference. High expression of all 3 kinases was associated with relatively poor prognosis in patients with osteosarcoma. Conclusions: Our results not only offer potential therapeutic kinase targets in osteosarcoma but also provide a paradigm for functional genetic screening by using a CRISPR-Cas9 library, including target design, library construction, screening workflow, data analysis, and functional validation. -
Transcriptomic Analysis of Native Versus Cultured Human and Mouse Dorsal Root Ganglia Focused on Pharmacological Targets Short
bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Transcriptomic analysis of native versus cultured human and mouse dorsal root ganglia focused on pharmacological targets Short title: Comparative transcriptomics of acutely dissected versus cultured DRGs Andi Wangzhou1, Lisa A. McIlvried2, Candler Paige1, Paulino Barragan-Iglesias1, Carolyn A. Guzman1, Gregory Dussor1, Pradipta R. Ray1,#, Robert W. Gereau IV2, # and Theodore J. Price1, # 1The University of Texas at Dallas, School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, 800 W Campbell Rd. Richardson, TX, 75080, USA 2Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine # corresponding authors [email protected], [email protected] and [email protected] Funding: NIH grants T32DA007261 (LM); NS065926 and NS102161 (TJP); NS106953 and NS042595 (RWG). The authors declare no conflicts of interest Author Contributions Conceived of the Project: PRR, RWG IV and TJP Performed Experiments: AW, LAM, CP, PB-I Supervised Experiments: GD, RWG IV, TJP Analyzed Data: AW, LAM, CP, CAG, PRR Supervised Bioinformatics Analysis: PRR Drew Figures: AW, PRR Wrote and Edited Manuscript: AW, LAM, CP, GD, PRR, RWG IV, TJP All authors approved the final version of the manuscript. 1 bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Human Kinome Profiling Identifies a Requirement for AMP-Activated
Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection Laura J. Terrya, Livia Vastagb,1, Joshua D. Rabinowitzb, and Thomas Shenka,2 aDepartment of Molecular Biology and bDepartment of Chemistry and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544 Contributed by Thomas Shenk, January 11, 2012 (sent for review December 29, 2011) Human cytomegalovirus (HCMV) modulates numerous cellular (7). Thus, the connections between AMPK activity and metabolic signaling pathways. Alterations in signaling are evident from the changes during HCMV infection have remained unclear. broad changes in cellular phosphorylation that occur during HCMV We confirmed the requirement for AMPK during infection, infection and from the altered activity of multiple kinases. Here we and we show that an AMPK antagonist, compound C, blocks report a comprehensive RNAi screen, which predicts that 106 cellular HCMV-induced changes to glycolysis and inhibits viral gene kinases influence growth of the virus, most of which were not expression. These studies argue that AMPK or a related, com- previously linked to HCMV replication. Multiple elements of the pound C-sensitive kinase is an essential contributor to metabolic AMP-activated protein kinase (AMPK) pathway scored in the screen. changes initiated by HCMV and provide unique insight into As a regulator of carbon and nucleotide metabolism, AMPK is poised potential antiviral strategies. to activate many of the metabolic pathways induced by HCMV infection. An AMPK inhibitor, compound C, blocked a substantial Results portion of HCMV-induced metabolic changes, inhibited the accumu- HumanKinomeScreenIdentifies Putative Effectors of HCMV Replication. lation of all HCMV proteins tested, and markedly reduced the We conducted an siRNA screen of the human kinome to perform an production of infectious progeny. -
Support Info
Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2014 Supporting Information Design and synthesis of pyrrole–5-(2,6-dichlorobenzyl)sulfonylindolin-2-ones with C- 3’ side chains as potent Met kinase inhibitors Chia-Wei Liu,a Chun-Liang Lai,a Yu-Hsiang Lin,a Li-Wei Teng,a Sheng-chuan Yang,a Win-Yin Wei,a Shu Fu Lin,a Ju-Ying Yang,a Hung-Jyun Huang,a Ru-Wen Wang,a Chao-Cheng Chiang,a Mei-Hui Lee,a Yu- Chuan Wang,b Shih-Hsien Chuang,a Jia-Ming Chang,a Ying-Shuan E. Lee,a and Jiann-Jyh Huang*a,b aDevelopment Center for Biotechnology, No. 101, Lane 169, Kangning St., Xizhi District, New Taipei City 22180, Taiwan bDepartment of Applied Chemistry, National Chiayi University, No. 300, Syuefu Rd., Chiayi City 60004, Taiwan *Corresponding Author. Tel.: +886 5 271 7959; Fax: +886 5 271 7901. E-mail address: [email protected] (J.-J. Huang) Table of Contents: Page Supporting Figure. Ligplot diagrams of the ATP binding site of Met S2 complexed with compounds 2 and 20. Supporting Table. Kinase profiling data of compound 20. S3 References S10 - S1 - Supporting Figure. Ligplot diagrams1 of the ATP binding site of Met complexed with compounds 2 and 20: (A) Met with 2, and (B) Met with 20. - S2 - Supporting Table. Kinase profiling data of 20. Ambit KinomeScan Kinase Profiling (1.0 μM test concentration): Percentage of Percentage of Ambit Gene Symbol control (%) Ambit Gene Symbol control (%) 20 20 AAK1 68 ARK5 27 ABL1(E255K)-phosphorylated 85 ASK1 100 ABL1(F317I)-nonphosphorylated 78 ASK2 67 -
Profiling Data
Compound Name DiscoveRx Gene Symbol Entrez Gene Percent Compound Symbol Control Concentration (nM) JNK-IN-8 AAK1 AAK1 69 1000 JNK-IN-8 ABL1(E255K)-phosphorylated ABL1 100 1000 JNK-IN-8 ABL1(F317I)-nonphosphorylated ABL1 87 1000 JNK-IN-8 ABL1(F317I)-phosphorylated ABL1 100 1000 JNK-IN-8 ABL1(F317L)-nonphosphorylated ABL1 65 1000 JNK-IN-8 ABL1(F317L)-phosphorylated ABL1 61 1000 JNK-IN-8 ABL1(H396P)-nonphosphorylated ABL1 42 1000 JNK-IN-8 ABL1(H396P)-phosphorylated ABL1 60 1000 JNK-IN-8 ABL1(M351T)-phosphorylated ABL1 81 1000 JNK-IN-8 ABL1(Q252H)-nonphosphorylated ABL1 100 1000 JNK-IN-8 ABL1(Q252H)-phosphorylated ABL1 56 1000 JNK-IN-8 ABL1(T315I)-nonphosphorylated ABL1 100 1000 JNK-IN-8 ABL1(T315I)-phosphorylated ABL1 92 1000 JNK-IN-8 ABL1(Y253F)-phosphorylated ABL1 71 1000 JNK-IN-8 ABL1-nonphosphorylated ABL1 97 1000 JNK-IN-8 ABL1-phosphorylated ABL1 100 1000 JNK-IN-8 ABL2 ABL2 97 1000 JNK-IN-8 ACVR1 ACVR1 100 1000 JNK-IN-8 ACVR1B ACVR1B 88 1000 JNK-IN-8 ACVR2A ACVR2A 100 1000 JNK-IN-8 ACVR2B ACVR2B 100 1000 JNK-IN-8 ACVRL1 ACVRL1 96 1000 JNK-IN-8 ADCK3 CABC1 100 1000 JNK-IN-8 ADCK4 ADCK4 93 1000 JNK-IN-8 AKT1 AKT1 100 1000 JNK-IN-8 AKT2 AKT2 100 1000 JNK-IN-8 AKT3 AKT3 100 1000 JNK-IN-8 ALK ALK 85 1000 JNK-IN-8 AMPK-alpha1 PRKAA1 100 1000 JNK-IN-8 AMPK-alpha2 PRKAA2 84 1000 JNK-IN-8 ANKK1 ANKK1 75 1000 JNK-IN-8 ARK5 NUAK1 100 1000 JNK-IN-8 ASK1 MAP3K5 100 1000 JNK-IN-8 ASK2 MAP3K6 93 1000 JNK-IN-8 AURKA AURKA 100 1000 JNK-IN-8 AURKA AURKA 84 1000 JNK-IN-8 AURKB AURKB 83 1000 JNK-IN-8 AURKB AURKB 96 1000 JNK-IN-8 AURKC AURKC 95 1000 JNK-IN-8 -
Kinaseseeker™ Full-Length Panel (112 Wild-Type Kinases)
KinaseSeeker™ Full-Length Panel (112 Wild-Type Kinases) Kinase Group Kinase Group ABL1 full-length TK DDR1 intracellular module TK ACVR1 intracellular module TKL DDR2 intracellular module TK AKT1 full-length AGC EGFR intracellular module TK AKT2 full-length AGC EPHA1 intracellular module TK AKT3 full-length AGC EPHA2 intracellular module TK AMPKa1 full-length CAMK EPHA3 intracellular module TK BLK full-length TK EPHA4 intracellular module TK BTK full-length TK EPHA5 intracellular module TK CAMK1D full-length CAMK EPHA6 intracellular module TK CAMK1G full-length CAMK EPHA7 intracellular module TK CAMK2A full-length CAMK EPHA8 intracellular module TK CAMK2B full-length CAMK EPHB3 intracellular module TK CAMK2D full-length CAMK EPHB4 intracellular module TK CAMK2G full-length CAMK ERBB2 intracellular module TK CAMKK1 full-length Other ERBB4 intracellular module TK CAMKK2 full-length Other FAK full-length TK CASK full-length CAMK FGFR2 intracellular module TK CDKL5 full-length CMGC FGFR3 intracellular module TK CK1d full-length CK1 FGR full-length TK CLK1 full-length CMGC FLT1 intracellular module TK CLK2 full-length CMGC FLT2 intracellular module TK CLK3 full-length CMGC FLT4 intracellular module TK CSF1R intracellular module TK FRK full-length TK CSK full-length TK FYN full-length TK DAPK1 full-length CAMK GRK7 full-length AGC Legend: Full-Length: Construct contains Full-length kinase Intracellular Module: Construct contains Cytoplasmic Region in Receptor Tyrosine Kinases Page 1 of 3 KinaseSeeker™ Full-Length Panel (112 Wild-Type Kinases) -
Informationpackage.Pdf
TABLE OF CONTENTS Sample Preparation PDF Page No. 1. Introduction ……………………………………………………………………………………….……. 3 2. Quantity of lysate required …………………………………………………………………………… 5 3. Preparation of cell lysates A. Adherent cells ………………………………………………………………………..…….……. 6 B. Suspension cells ………………………………………………………………………...……… 6 4. Preparation of cell pellets …………………………………………………………………….……… 7 5. Tissue preparation ……………………………………………………………………………………. 7 6. Sample buffer preparation …………………………………………………………………………… 8 Shipping & Pricing 7. Preparation for storage and shipping of samples ……………………………………………..…. 8 8. Shipping information ………………………………………………………………………………….. 8 9. Pricing information ……………………………………………………………………………………. 9 Description of Follow Up Services 10. Follow up services ……………………………………………………………………………………. 9 11. Forms to be completed ………………………………………………………………………………. 10 Sample Buffer Protocol 12. Appendix A - KinetworksTM Sample Buffer protocol ………………………………………………. 15 KinetworksTM Phospho-Site Screening Services 13. Appendix B - List of 38 phosphorylation sites in KPSS-1.3 - Broad Signalling Pathway ….… 16 14. Appendix C - List of 44 phosphorylation sites in KPSS-10.1 - Cell Cycle Status Screen….... 17 15. Appendix D - List of 37 phosphorylation sites in KPSS-11.0 - Protein Kinase Screen …....... 18 16. Appendix E - List of 40 phosphorylation sites in KPSS-12.1 - Substrates of Kinases Screen 19 KinetworksTM Expression Level Profiling Services 17. Appendix F - List of 76 proteins tracked in KPKS-1.2 Screen – Protein Kinase Screen ....… 20 18. Appendix G - List -
IRAK-M Associates with Susceptibility to Adult-Onset Asthma and Promotes Chronic Airway Inflammation
IRAK-M Associates with Susceptibility to Adult-Onset Asthma and Promotes Chronic Airway Inflammation This information is current as Yi Liu, Mingqiang Zhang, Lili Lou, Lun Li, Youming of September 28, 2021. Zhang, Wei Chen, Weixun Zhou, Yan Bai and Jinming Gao J Immunol published online 7 January 2019 http://www.jimmunol.org/content/early/2019/01/04/jimmun ol.1800712 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2019/01/04/jimmunol.180071 Material 2.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 28, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published January 7, 2019, doi:10.4049/jimmunol.1800712 The Journal of Immunology IRAK-M Associates with Susceptibility to Adult-Onset Asthma and Promotes Chronic Airway Inflammation Yi Liu,*,†,1 Mingqiang Zhang,*,1 Lili Lou,* Lun Li,* Youming Zhang,‡ Wei Chen,x Weixun Zhou,{ Yan Bai,‖ and Jinming Gao* IL-1R–associated kinase (IRAK)-M regulates lung immunity during asthmatic airway inflammation. -
TSPY and Its X-Encoded Homologue Interact with Cyclin B but Exert Contrasting Functions on Cyclin-Dependent Kinase 1 Activities
Oncogene (2008) 27, 6141–6150 & 2008 Macmillan Publishers Limited All rights reserved 0950-9232/08 $32.00 www.nature.com/onc ORIGINAL ARTICLE TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities Y Li and Y-F Chris Lau Department of Medicine, VA Medical Center, University of California, San Francisco, San Francisco, CA, USA Testis-specific protein Y-encoded (TSPY) is the putative in XY sex-reversed patients and intersex individuals to gene for the gonadoblastoma locus on the Y chromosome gonadoblastoma development (Page, 1987; Lau, 1999). (GBY). TSPY and an X-homologue, TSPX, harbor a The 2.8-kbTSPY transcriptional unit is embedded in a conserved domain, designated as SET/NAP domain, but 20.4-kbDNA fragment that is repeated tandemly at the differ at their C termini. Ectopic expression of TSPY critical region for GBY on the short arm, proximal to accelerates cell proliferation byabbreviating the G 2/M the centromere, of the human Y chromosome (Skaletsky stage, whereas overexpression of TSPX retards cells et al., 2003). The number of TSPY repeats varies from at the same stage of the cell cycle. Previous studies B23 to 64 among phenotypically normal individual demonstrated that the SET oncoprotein is capable males (Repping et al., 2006), but could change under of binding to cyclin B. Using various protein interaction certain disease conditions (Vijayakumar et al., 2006), techniques, we demonstrated that TSPY and TSPX suggesting the possibility of genomic instability in this indeed bind competitivelyto cyclinB at their SET/NAP region of the chromosome. -
PCTK2 Protein Full-Length Recombinant Human Protein Expressed in Sf9 Cells
Catalog # Aliquot Size P10-34G-20 20 µg P10-34G-50 50 µg PCTK2 Protein Full-length recombinant human protein expressed in Sf9 cells Catalog # P10-34G Lot # Z1204 -3 Product Description Purity Recombinant full-length human PCTK2 (CDK17) was expressed by baculovirus in Sf9 insect cells using an N- terminal GST tag. This gene accession number is NM_002595 . The purity of PCTK2 protein was determined to be >75% by Gene Aliases densitometry. Approx. MW 88 kDa . PCTAIRE2; PCTK2 Formulation Recombinant protein stored in 50mM Tris-HCl, pH 7.5, 50mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol. Storage and Stability Store product at –70 oC. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles. Scientific Background PCTK2 (CDK17) or cyclin-dependent kinase 17 belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. PCTK2 has similarity to a rat protein that is thought to play a role in terminally differentiated neurons (1). The identification of a large family of cdc2-related kinases PCTK2 Protein opens the possibility of combinatorial regulation of the Full-length recombinant human protein expressed in Sf9 cells cell cycle together with the emerging large family of cyclins (2). Catalog # P10-34G Lot # Z1204-3 References Purity >75% Concentration 0.1 µ g/ µl 1. Hirose T. et.al: PCTAIRE 2, a Cdc2-related serine/threonine Stability 1yr At –70 oC from date of shipment kinase, is predominantly expressed in terminally Storage & Shipping Store product at –70 oC.