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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 -
The Drug Sensitivity and Resistance Testing (DSRT) Approach
A phenotypic screening and machine learning platform eciently identifies triple negative breast cancer-selective and readily druggable targets Prson Gautam 1 Alok Jaiswal 1 Tero Aittokallio 1, 2 Hassan Al Ali 3 Krister Wennerberg 1,4 Identifying eective oncogenic targets is challenged by the complexity of genetic alterations in 1Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Finland cancer and their poorly understood relation to cell function and survival. There is a need for meth- Current kinome coverage of kinase inhibitors in TNBC exhibit diverse kinase dependencies MFM-223 is selectively addicted to FGFR2 2Department of Mathematics and Statistics, University of Turku, Finland 3The Miami Project to Cure Paralysis, Peggy and Harold Katz Family Drug Discovery Center, A A Sylvester Comprehensive Cancer Center, and Department of Neurological Surgery and Medicine ods that rapidly and accurately identify “pharmacologically eective” targets without the require- clinical evaluation TN Kinases MFM-223 CAL-120 MDA-MB-231 TNBC TNBC TNBC TNBC TNBC TNBC HER2+ 100 University of Miami Miller School of Medicine, Miami, FL 33136, USA. non- HER2+ FGFR1 0.97 0.00 0.00 MFM-223 BL1 BL2 M MSL IM LAR ER+, PR+ 50 ment for priori knowledge of complex signaling networks. We developed an approach that uses ma- cancerous FGFR2 56.46 0.00 0.00 CAL-120 25 4 MDA-MB-231 Biotech Research & Innovation Centre (BRIC) and Novo Nordisk Foundation Center HCC1937 CAL-85-1 CAL-120 MDA-MB-231 DU4475 CAL-148 MCF-10A SK-BR-3 BT-474 FGFR3 25.10 0.00 0.00 0 chine learning to relate results from unbiased phenotypic screening of kinase inhibitors to their bio- for Stem Cell Biology (DanStem), University of Copenhagen, Denmark HCC1599 HDQ-P1 BT-549 MDA-MB-436 MFM-223 FGFR4 0.00 0.00 0.00 MAXIS*Bk Clinical status MDA-MB-468 CAL-51 Hs578T MDA-MB-453 score chemical activity data. -
Clustering of the Structures of Protein Kinase Activation Loops
bioRxiv preprint doi: https://doi.org/10.1101/395723; this version posted August 19, 2018. 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-NC 4.0 International license. Clustering of the structures of protein kinase activation loops: A new nomenclature for active and inactive kinase structures Vivek Modi Roland L. Dunbrack, Jr.* Institute for Cancer Research Fox Chase Cancer Center Philadelphia PA 19111 *[email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/395723; this version posted August 19, 2018. 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-NC 4.0 International license. Abstract TarGeting protein kinases is an important strateGy for intervention in cancer. Inhibitors are directed at the conserved active conformation or a variety of inactive conformations. While attempts have been made to classify these conformations, a structurally rigorous cataloGue of states has not been achieved. The kinase activation loop is crucial for catalysis and beGins with the conserved DFGmotif (Asp-Phe-Gly). This motif is observed in two major classes of conformations, DFGin - an ensemble of active and inactive conformations where the Phe residue is in contact with the C-helix of the N-terminal lobe, and DFGout - an inactive form where Phe occupies the ATP site exposinG the C-helix pocket. -
Epithelial Ovarian Cancer: Searching for New Modulators of Drug Resistance
UNIVERSITÀ DEGLI STUDI DI UDINE Dipartimento di scienze mediche e biologiche PhD COURSE IN BIOMEDICAL SCIENCES AND BIOTECHNOLOGY XXIX cycle PhD THESIS Epithelial Ovarian Cancer: searching for new modulators of drug resistance. PhD student Supervisor Prof. Carlo Ennio Michele Pucillo Valentina Ranzuglia Co-supervisors Dr. Gustavo Baldassarre Dr. Monica Schiappacassi PhD coordinator Prof. Claudio Brancolini Academic year 2015/2016 This PhD work was done at Centro di Riferimento Oncologico (CRO, National Cancer Institute ) of Aviano, in the Division of Experimental Oncology 2 directed by Dr. Gustavo Baldassarre. i Table of contents Abstract 3 1. Introduction 4 1.1 Epithelial Ovarian Cancer 4 1.1.1 Platinum resistance 5 1.2 Functional Genomic Screening 8 1.3 Serum and glucocorticoid-regulated kinases 9 1.3.1 SGK structure 10 1.3.2 SGK activation and regulation 11 1.3.3 Role of SGKs in regulation of molecular and cellular functions 13 1.3.4 Serum- and glucocorticoid-regulated kinases in cancer 15 1.4 Autophagy 17 2.Aim of the study 21 3.Results 22 3.1 Identification of SGK2 as a mediator of platinum sensitivity in EOC cells. 22 3.2 SGK2 silencing sensitizes EOC cells to platinum. 23 3.3 SGK2 overexpression confers an increased resistance to platinum drug. 25 3.4 SGK2-overexpressing cells present an increased in vitro and in vivo growth 26 rate 3.5 SGK2 kinase activity is involved in EOC sensitivity to platinum treatment. 28 3.6 The SGK1/SGK2 kinase inhibitor, GSK650394, reduces cell viability in 29 combination with platinum. 3.7 GSK650394 is able to make SGK2-expressing cells more sensitive to platinum. -
AGC Kinases in Mtor Signaling, in Mike Hall and Fuyuhiko Tamanoi: the Enzymes, Vol
Provided for non-commercial research and educational use only. Not for reproduction, distribution or commercial use. This chapter was originally published in the book, The Enzymes, Vol .27, published by Elsevier, and the attached copy is provided by Elsevier for the author's benefit and for the benefit of the author's institution, for non-commercial research and educational use including without limitation use in instruction at your institution, sending it to specific colleagues who know you, and providing a copy to your institution’s administrator. All other uses, reproduction and distribution, including without limitation commercial reprints, selling or licensing copies or access, or posting on open internet sites, your personal or institution’s website or repository, are prohibited. For exceptions, permission may be sought for such use through Elsevier's permissions site at: http://www.elsevier.com/locate/permissionusematerial From: ESTELA JACINTO, AGC Kinases in mTOR Signaling, In Mike Hall and Fuyuhiko Tamanoi: The Enzymes, Vol. 27, Burlington: Academic Press, 2010, pp.101-128. ISBN: 978-0-12-381539-2, © Copyright 2010 Elsevier Inc, Academic Press. Author's personal copy 7 AGC Kinases in mTOR Signaling ESTELA JACINTO Department of Physiology and Biophysics UMDNJ-Robert Wood Johnson Medical School, Piscataway New Jersey, USA I. Abstract The mammalian target of rapamycin (mTOR), a protein kinase with homology to lipid kinases, orchestrates cellular responses to growth and stress signals. Various extracellular and intracellular inputs to mTOR are known. mTOR processes these inputs as part of two mTOR protein com- plexes, mTORC1 or mTORC2. Surprisingly, despite the many cellular functions that are linked to mTOR, there are very few direct mTOR substrates identified to date. -
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 -
PRKCQ Promotes Oncogenic Growth and Anoikis Resistance of a Subset
Byerly et al. Breast Cancer Research (2016) 18:95 DOI 10.1186/s13058-016-0749-6 RESEARCH ARTICLE Open Access PRKCQ promotes oncogenic growth and anoikis resistance of a subset of triple- negative breast cancer cells Jessica Byerly1†, Gwyneth Halstead-Nussloch1†, Koichi Ito1, Igor Katsyv3 and Hanna Y. Irie1,2* Abstract Background: The protein kinase C (PKC) family comprises distinct classes of proteins, many of which are implicated in diverse cellular functions. Protein tyrosine kinase C theta isoform (PRKCQ)/PKCθ, a member of the novel PKC family, may have a distinct isoform-specific role in breast cancer. PKCθ is preferentially expressed in triple-negative breast cancer (TNBC) compared to other breast tumor subtypes. We hypothesized that PRKCQ/PKCθ critically regulates growth and survival of a subset of TNBC cells. Methods: To elucidate the role of PRKCQ/PKCθ in regulating growth and anoikis resistance, we used both gain and loss of function to modulate expression of PRKCQ. We enhanced expression of PKCθ (kinase-active or inactive) in non-transformed breast epithelial cells (MCF-10A) and assessed effects on epidermal growth factor (EGF)- independent growth, anoikis, and migration. We downregulated expression of PKCθ in TNBC cells, and determined effects on in vitro and in vivo growth and survival. TNBC cells were also treated with a small molecule inhibitor to assess requirement for PKCθ kinase activity in the growth of TNBC cells. Results: PRKCQ/PKCθ can promote oncogenic phenotypes when expressed in non-transformed MCF-10A mammary epithelial cells; PRKCQ/PKCθ enhances anchorage-independent survival, growth-factor-independent proliferation, and migration. PKCθ expression promotes retinoblastoma (Rb) phosphorylation and cell-cycle progression under growth factor-deprived conditions that typically induce cell-cycle arrest of MCF-10A breast epithelial cells. -
SGK3 Sirna Set I Sirna Duplexes Targeted Against Three Exon Regions
Catalog # Aliquot Size S08-911-05 3 x 5 nmol S08-911-20 3 x 20 nmol S08-911-50 3 x 50 nmol SGK3 siRNA Set I siRNA duplexes targeted against three exon regions Catalog # S08-911 Lot # Z2085-77 Specificity Formulation SGK3 siRNAs are designed to specifically knock-down The siRNAs are supplied as a lyophilized powder and human SGK3 expression. shipped at room temperature. Product Description Reconstitution Protocol SGK3 siRNA is a pool of three individual synthetic siRNA Briefly centrifuge the tubes (maximum RCF 4,000g) to duplexes designed to knock-down human SGK3 mRNA collect lyophilized siRNA at the bottom of the tube. expression. Each siRNA is 19-25 bases in length. The gene Resuspend the siRNA in 50 µl of DEPC-treated water accession number is NM_013257. (supplied by researcher), which results in a 1x stock solution (10 µM). Gently pipet the solution 3-5 times to mix Gene Aliases and avoid the introduction of bubbles. Optional: aliquot CISK, SGKL 1x stock solutions for storage. Storage and Stability Related Products The lyophilized powder is stable for at least 4 weeks at room temperature. It is recommended that the Product Name Catalog Number lyophilized and resuspended siRNAs are stored at or SGK1, Active S06-11G below -20oC. After resuspension, siRNA stock solutions ≥2 SGK2, Active S07-10G µM can undergo up to 50 freeze-thaw cycles without SGK3, Active S08-10G significant degradation. For long-term storage, it is SGK1, Unactive S06-15G recommended that the siRNA is stored at -70oC. For most SGK2, Unactive S07-14G favorable performance, avoid repeated handling and SGK3, Unactive S08-14G multiple freeze/thaw cycles. -
Kinase Profiling Book
Custom and Pre-Selected Kinase Prof iling to f it your Budget and Needs! As of July 1, 2021 19.8653 mm 128 196 12 Tyrosine Serine/Threonine Lipid Kinases Kinases Kinases Carna Biosciences, Inc. 2007 Carna Biosciences, Inc. Profiling Assays available from Carna Biosciences, Inc. As of July 1, 2021 Page Kinase Name Assay Platform Page Kinase Name Assay Platform 4 ABL(ABL1) MSA 21 EGFR[T790M/C797S/L858R] MSA 4 ABL(ABL1)[E255K] MSA 21 EGFR[T790M/L858R] MSA 4 ABL(ABL1)[T315I] MSA 21 EPHA1 MSA 4 ACK(TNK2) MSA 21 EPHA2 MSA 4 AKT1 MSA 21 EPHA3 MSA 5 AKT2 MSA 22 EPHA4 MSA 5 AKT3 MSA 22 EPHA5 MSA 5 ALK MSA 22 EPHA6 MSA 5 ALK[C1156Y] MSA 22 EPHA7 MSA 5 ALK[F1174L] MSA 22 EPHA8 MSA 6 ALK[G1202R] MSA 23 EPHB1 MSA 6 ALK[G1269A] MSA 23 EPHB2 MSA 6 ALK[L1196M] MSA 23 EPHB3 MSA 6 ALK[R1275Q] MSA 23 EPHB4 MSA 6 ALK[T1151_L1152insT] MSA 23 Erk1(MAPK3) MSA 7 EML4-ALK MSA 24 Erk2(MAPK1) MSA 7 NPM1-ALK MSA 24 Erk5(MAPK7) MSA 7 AMPKα1/β1/γ1(PRKAA1/B1/G1) MSA 24 FAK(PTK2) MSA 7 AMPKα2/β1/γ1(PRKAA2/B1/G1) MSA 24 FER MSA 7 ARG(ABL2) MSA 24 FES MSA 8 AurA(AURKA) MSA 25 FGFR1 MSA 8 AurA(AURKA)/TPX2 MSA 25 FGFR1[V561M] MSA 8 AurB(AURKB)/INCENP MSA 25 FGFR2 MSA 8 AurC(AURKC) MSA 25 FGFR2[V564I] MSA 8 AXL MSA 25 FGFR3 MSA 9 BLK MSA 26 FGFR3[K650E] MSA 9 BMX MSA 26 FGFR3[K650M] MSA 9 BRK(PTK6) MSA 26 FGFR3[V555L] MSA 9 BRSK1 MSA 26 FGFR3[V555M] MSA 9 BRSK2 MSA 26 FGFR4 MSA 10 BTK MSA 27 FGFR4[N535K] MSA 10 BTK[C481S] MSA 27 FGFR4[V550E] MSA 10 BUB1/BUB3 MSA 27 FGFR4[V550L] MSA 10 CaMK1α(CAMK1) MSA 27 FGR MSA 10 CaMK1δ(CAMK1D) MSA 27 FLT1 MSA 11 CaMK2α(CAMK2A) MSA 28 -
Silencing of Lncrna H19 Enhances the Sensitivity to X-Rays and Carbon-Ions Through the Mir-130A-3P /WNK3 Signal Axis in Non-Small-Cell Lung Cancer Cells
Silencing of lncRNA H19 Enhances the Sensitivity to X-rays and Carbon-Ions Through the miR-130a-3p /WNK3 Signal Axis in Non-Small-Cell Lung Cancer Cells Xueshan Zhao Lanzhou University First Aliated Hospital https://orcid.org/0000-0002-1194-7617 Xiaodong Jin Institute of Modern Physics Chinese Academy of Sciences Qiuning Zhang Institute of Modern Physics Chinese Academy of Sciences Ruifeng Liu Institute of Modern Physics Chinese Academy of Sciences Hongtao Luo Institute of Modern Physics Chinese Academy of Sciences Zhen Yang Lanzhou University School of Basic Medical Sciences Yichao Geng Lanzhou University First Aliated Hospital Shuangwu Feng Lanzhou University First Aliated Hospital Chengcheng Li Lanzhou University First Aliated Hospital Lina Wang Lanzhou University First Aliated Hospital Xiaohu Wang ( [email protected] ) Lanzhou University First Aliated Hospital Qiang Li Institute of Modern Physics Chinese Academy of Sciences Research Article Keywords: LncRNA H19, MiR-130a-3p, WNK3, Non-small-cell lung cancer, Radiotherapy Posted Date: August 10th, 2021 Page 1/20 DOI: https://doi.org/10.21203/rs.3.rs-768334/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/20 Abstract Background: LncRNA H19 was believed to act as an oncogene in various types of tumors and was considered to be a therapeutic target and diagnosis marker. However, the role of lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells was unknown. However, the effects of lncRNA H19 on radiosensitivity of NSCLC were not clear. Methods: The expression proles of lncRNAs were explored via transcriptome sequencing in NSCLC. -
Key Genes Regulating Skeletal Muscle Development and Growth in Farm Animals
animals Review Key Genes Regulating Skeletal Muscle Development and Growth in Farm Animals Mohammadreza Mohammadabadi 1 , Farhad Bordbar 1,* , Just Jensen 2 , Min Du 3 and Wei Guo 4 1 Department of Animal Science, Faculty of Agriculture, Shahid Bahonar University of Kerman, Kerman 77951, Iran; [email protected] 2 Center for Quantitative Genetics and Genomics, Aarhus University, 8210 Aarhus, Denmark; [email protected] 3 Washington Center for Muscle Biology, Department of Animal Sciences, Washington State University, Pullman, WA 99163, USA; [email protected] 4 Muscle Biology and Animal Biologics, Animal and Dairy Science, University of Wisconsin-Madison, Madison, WI 53558, USA; [email protected] * Correspondence: [email protected] Simple Summary: Skeletal muscle mass is an important economic trait, and muscle development and growth is a crucial factor to supply enough meat for human consumption. Thus, understanding (candidate) genes regulating skeletal muscle development is crucial for understanding molecular genetic regulation of muscle growth and can be benefit the meat industry toward the goal of in- creasing meat yields. During the past years, significant progress has been made for understanding these mechanisms, and thus, we decided to write a comprehensive review covering regulators and (candidate) genes crucial for muscle development and growth in farm animals. Detection of these genes and factors increases our understanding of muscle growth and development and is a great help for breeders to satisfy demands for meat production on a global scale. Citation: Mohammadabadi, M.; Abstract: Farm-animal species play crucial roles in satisfying demands for meat on a global scale, Bordbar, F.; Jensen, J.; Du, M.; Guo, W. -
Protein Kinase C As a Paradigm Alexandra C
Biochem. J. (2003) 370, 361–371 (Printed in Great Britain) 361 REVIEW ARTICLE Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm Alexandra C. NEWTON1 Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093-0640, U.S.A. Phosphorylation plays a central role in regulating the activation down-regulation of PKC as a paradigm for how these sites and signalling lifetime of protein kinases A, B (also known as control the function of the ABC kinases. Akt) and C. These kinases share three conserved phosphorylation motifs: the activation loop segment, the turn motif and the Key words: phosphoinositide 3-kinase, phosphoinositide-depen- hydrophobic motif. This review focuses on how phosphorylation dent kinase-1 (PDK-1), phosphorylation motif, protein kinase A at each of these sites regulates the maturation, signalling and (PKA), protein kinase B (PKB)\Akt, protein kinase C (PKC). INTRODUCTION by phosphorylation as a paradigm for control of ABC kinase function by phosphorylation. Almost half a century ago Krebs, Graves and Fischer reported b that the first discovered protein kinase, phosphorylase kinase, ARCHITECTURE OF ABC KINASES was, itself, activated by phosphorylation [1]. Two decades later, Fischer and colleagues showed that the kinase that phosphory- Protein kinases A, B\Akt and C have in common a conserved lates phosphorylase kinase, later named protein kinase A (PKA), kinase core whose function is regulated allosterically by a was also phosphorylated [2]. Reversible control by phosphory- corresponding regulatory moiety (Figure 1). In the case of PKA, lation\dephosphorylation is now firmly established as a fun- the regulatory moiety is a separate polypeptide, whereas the damental mechanism for regulating the function of most of the regulatory determinants are on the same polypeptide as the 500 or so members of the mammalian protein kinase superfamily.