R Graphics Output

Total Page:16

File Type:pdf, Size:1020Kb

R Graphics Output TNF signaling pathway all genes sink node genes ● ●● ●● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ●●● ● ●● ● ● ● ● ● ● ●● ●● ● ● ● ● ●● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ●● ● ● ●● ●●● ●●● ●●● ● ● ● ●●● ● ●●● ● maximum = 3 maximum = 2 2 1 s> 10 0 <log −1 −2 2 1 x a m s 0 10 log −1 −2 group 1 group 2 group 3 group 4 group 5 group 6 group 7 group 8 TNF_signaling_pathway genes with data CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway sink nodes CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway group 1 CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway group 2 CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway group 3 CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway group 4 CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway group 5 CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway group 6 CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway group 7 CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1 TNF_signaling_pathway group 8 CASP10 CCL2 CCL5 CCL20 CASP7 FADD CXCL1 CXCL1 CXCL1 CASP3 CASP8 CXCL5 CXCL10 CX3CL1 CSF1 CSF2 BIRC2 ITCH CFLAR FAS IL18R1 JAG1 MAP3K5 IL1B IL6 IL15 LIF LTA TAB1 MAP2K7 MAPK8 FOS BCL3 NFKBIA SOCS3 TNFAIP3 TRAF1 TRAF2 MAP3K7 TNF TNFRSF1A TRADD RIPK1 MAP2K3 MAPK14 CEBPB MAP3K8 NFKB1 RPS6KA4 CREB3 BAG4 MAP3K14 MAP2K1 MAPK1 FOS JUN JUNB MMP3 MMP9 MMP14 IKBKB NFKBIA CHUK EDN1 VEGFC IKBKG NFKB1 NOD2 RIPK1 RIPK3 MLKL PGAM5 ICAM1 SELE VCAM1 DNM1L PGAM5 PTGS2 PIK3CA AKT3 NFKB1 MAP3K14 CHUK NFKBIA TRAF1 LTA TNFRSF1B TRAF2 BIRC2 RIPK1 MAP2K3 MAPK14 TRAF3 DAB2IP MAPK8 JUN IRF1 IFNB1.
Recommended publications
  • 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
    [Show full text]
  • Supplementary Material DNA Methylation in Inflammatory Pathways Modifies the Association Between BMI and Adult-Onset Non- Atopic
    Supplementary Material DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non- Atopic Asthma Ayoung Jeong 1,2, Medea Imboden 1,2, Akram Ghantous 3, Alexei Novoloaca 3, Anne-Elie Carsin 4,5,6, Manolis Kogevinas 4,5,6, Christian Schindler 1,2, Gianfranco Lovison 7, Zdenko Herceg 3, Cyrille Cuenin 3, Roel Vermeulen 8, Deborah Jarvis 9, André F. S. Amaral 9, Florian Kronenberg 10, Paolo Vineis 11,12 and Nicole Probst-Hensch 1,2,* 1 Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; [email protected] (A.J.); [email protected] (M.I.); [email protected] (C.S.) 2 Department of Public Health, University of Basel, 4001 Basel, Switzerland 3 International Agency for Research on Cancer, 69372 Lyon, France; [email protected] (A.G.); [email protected] (A.N.); [email protected] (Z.H.); [email protected] (C.C.) 4 ISGlobal, Barcelona Institute for Global Health, 08003 Barcelona, Spain; [email protected] (A.-E.C.); [email protected] (M.K.) 5 Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain 6 CIBER Epidemiología y Salud Pública (CIBERESP), 08005 Barcelona, Spain 7 Department of Economics, Business and Statistics, University of Palermo, 90128 Palermo, Italy; [email protected] 8 Environmental Epidemiology Division, Utrecht University, Institute for Risk Assessment Sciences, 3584CM Utrecht, Netherlands; [email protected] 9 Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College, SW3 6LR London, UK; [email protected] (D.J.); [email protected] (A.F.S.A.) 10 Division of Genetic Epidemiology, Medical University of Innsbruck, 6020 Innsbruck, Austria; [email protected] 11 MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, W2 1PG London, UK; [email protected] 12 Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy * Correspondence: [email protected]; Tel.: +41-61-284-8378 Int.
    [Show full text]
  • The Mtor Substrate S6 Kinase 1 (S6K1)
    The Journal of Neuroscience, July 26, 2017 • 37(30):7079–7095 • 7079 Cellular/Molecular The mTOR Substrate S6 Kinase 1 (S6K1) Is a Negative Regulator of Axon Regeneration and a Potential Drug Target for Central Nervous System Injury X Hassan Al-Ali,1,2,3* Ying Ding,5,6* Tatiana Slepak,1* XWei Wu,5 Yan Sun,5,7 Yania Martinez,1 Xiao-Ming Xu,5 Vance P. Lemmon,1,3 and XJohn L. Bixby1,3,4 1Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33136, 2Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, Florida 33136, 3Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, 4Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida 33136, 5Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, 6Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China, and 7Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China Themammaliantargetofrapamycin(mTOR)positivelyregulatesaxongrowthinthemammaliancentralnervoussystem(CNS).Althoughaxon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a negative regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR’s positive effect on axon growth. In contrast to this expectation, we demon- strate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by twofold to threefold.
    [Show full text]
  • The Mtor Substrate S6 Kinase 1 (S6K1) Is a Negative Regulator of Axon Regeneration and a Potential Drug Target for Central Nervous System Injury
    This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. Research Articles: Cellular/Molecular The mTOR substrate S6 Kinase 1 (S6K1) is a negative regulator of axon regeneration and a potential drug target for Central Nervous System injury Hassan Al-Ali1,2,3, Ying Ding5,6, Tatiana Slepak1, Wei Wu5, Yan Sun5,7, Yania Martinez1, Xiao-Ming Xu5, V.P. Lemmon1,3 and J.l. Bixby1,3,4 1The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. 2Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 3Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA. 4Department of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. 5Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. 6Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. 7Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. DOI: 10.1523/JNEUROSCI.0931-17.2017 Received: 4 April 2017 Revised: 18 May 2017 Accepted: 27 May 2017 Published: 16 June 2017 Author contributions: H.A.-A., Y.D., T.S., W.W., Y.S., X.-M.X., V.P.L., and J.B. designed research; H.A.-A., Y.D., T.S., W.W., Y.S., and Y.M.
    [Show full text]
  • Activation of Diverse Signalling Pathways by Oncogenic PIK3CA Mutations
    ARTICLE Received 14 Feb 2014 | Accepted 12 Aug 2014 | Published 23 Sep 2014 DOI: 10.1038/ncomms5961 Activation of diverse signalling pathways by oncogenic PIK3CA mutations Xinyan Wu1, Santosh Renuse2,3, Nandini A. Sahasrabuddhe2,4, Muhammad Saddiq Zahari1, Raghothama Chaerkady1, Min-Sik Kim1, Raja S. Nirujogi2, Morassa Mohseni1, Praveen Kumar2,4, Rajesh Raju2, Jun Zhong1, Jian Yang5, Johnathan Neiswinger6, Jun-Seop Jeong6, Robert Newman6, Maureen A. Powers7, Babu Lal Somani2, Edward Gabrielson8, Saraswati Sukumar9, Vered Stearns9, Jiang Qian10, Heng Zhu6, Bert Vogelstein5, Ben Ho Park9 & Akhilesh Pandey1,8,9 The PIK3CA gene is frequently mutated in human cancers. Here we carry out a SILAC-based quantitative phosphoproteomic analysis using isogenic knockin cell lines containing ‘driver’ oncogenic mutations of PIK3CA to dissect the signalling mechanisms responsible for oncogenic phenotypes induced by mutant PIK3CA. From 8,075 unique phosphopeptides identified, we observe that aberrant activation of PI3K pathway leads to increased phosphorylation of a surprisingly wide variety of kinases and downstream signalling networks. Here, by integrating phosphoproteomic data with human protein microarray-based AKT1 kinase assays, we discover and validate six novel AKT1 substrates, including cortactin. Through mutagenesis studies, we demonstrate that phosphorylation of cortactin by AKT1 is important for mutant PI3K-enhanced cell migration and invasion. Our study describes a quantitative and global approach for identifying mutation-specific signalling events and for discovering novel signalling molecules as readouts of pathway activation or potential therapeutic targets. 1 McKusick-Nathans Institute of Genetic Medicine and Department of Biological Chemistry, Johns Hopkins University School of Medicine, 733 North Broadway, BRB 527, Baltimore, Maryland 21205, USA.
    [Show full text]
  • Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK & CLK Kinases
    Article Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK & CLK Kinases Nadège Loaëc 1,2, Eletta Attanasio 1, Benoît Villiers 1, Emilie Durieu 1, Tania Tahtouh 1, Morgane Cam 1, Rohan A. Davis 3, Aline Alencar 4, Mélanie Roué 5, Marie-Lise Bourguet-Kondracki 5, Peter Proksch 6, Emmanuelle Limanton 7, Solène Guiheneuf 7, François Carreaux 7,*, Jean-Pierre Bazureau 7,*, Michelle Klautau 4,* and Laurent Meijer 1,* 1 ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France; [email protected] (N.L.); [email protected] (E.A.); [email protected] (B.V.); [email protected] (E.D.); [email protected] (T.T.); [email protected] (M.C.) 2 Station Biologique de Roscoff, CNRS, ‘Protein Phosphorylation and Human Disease’ Group, Place G. Teissier, 29680 Roscoff, Bretagne, France 3 Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia; [email protected] 4 Universidade Federal do Rio de Janeiro, Instituto de Biologia—Departamento de Zoologia, Av. Carlos Chagas Filho 373-CCS-Bloco A-Sala A0-100, Ilha do Fundão, 21941-902 Rio de Janeiro, Brazil; [email protected] 5 Molécules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Muséum National d’ Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France; [email protected] (M.R.); [email protected] (M.-L.B.-K.) 6 Institut für Pharmazeutische Biologie und Biotechnologie, Universitätsstr. 1, 40225 Düsseldorf, Germany; [email protected] 7 Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât.
    [Show full text]
  • RPS6KA4 Antibody (C-Term) Purified Rabbit Polyclonal Antibody (Pab) Catalog # Ap21318b
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 RPS6KA4 Antibody (C-term) Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP21318b Specification RPS6KA4 Antibody (C-term) - Product Information Application WB,E Primary Accession O75676 Reactivity Human Host Rabbit Clonality polyclonal Isotype Rabbit Ig Calculated MW 85606 RPS6KA4 Antibody (C-term) - Additional Information Gene ID 8986 Other Names Ribosomal protein S6 kinase alpha-4, S6K-alpha-4, 90 kDa ribosomal protein S6 All lanes : Anti-RPS6KA4 Antibody (C-term) at kinase 4, Nuclear mitogen- and 1:2000 dilution Lane 1: Hela whole cell stress-activated protein kinase 2, Ribosomal lysates Lane 2: 293T/17 whole cell lysates protein kinase B, RSKB, RPS6KA4, MSK2 Lysates/proteins at 20 µg per lane. Secondary Goat Anti-Rabbit IgG, (H+L), Target/Specificity Peroxidase conjugated at 1/10000 dilution This RPS6KA4 antibody is generated from a rabbit immunized with a KLH conjugated Predicted band size : 86 kDa synthetic peptide between 692-725 amino Blocking/Dilution buffer: 5% NFDM/TBST. acids from the C-terminal region of human RPS6KA4. RPS6KA4 Antibody (C-term) - Background Dilution WB~~1:2000 Serine/threonine-protein kinase that is required for the mitogen or stress-induced Format phosphorylation of the transcription factors Purified polyclonal antibody supplied in PBS CREB1 and ATF1 and for the regulation of the with 0.09% (W/V) sodium azide. This transcription factor RELA, and that contributes antibody is purified through a protein A to gene activation by histone phosphorylation column, followed by peptide affinity and functions in the regulation of inflammatory purification.
    [Show full text]
  • PRODUCTS and SERVICES Target List
    PRODUCTS AND SERVICES Target list Kinase Products P.1-11 Kinase Products Biochemical Assays P.12 "QuickScout Screening Assist™ Kits" Kinase Protein Assay Kits P.13 "QuickScout Custom Profiling & Panel Profiling Series" Targets P.14 "QuickScout Custom Profiling Series" Preincubation Targets Cell-Based Assays P.15 NanoBRET™ TE Intracellular Kinase Cell-Based Assay Service Targets P.16 Tyrosine Kinase Ba/F3 Cell-Based Assay Service Targets P.17 Kinase HEK293 Cell-Based Assay Service ~ClariCELL™ ~ Targets P.18 Detection of Protein-Protein Interactions ~ProbeX™~ Stable Cell Lines Crystallization Services P.19 FastLane™ Structures ~Premium~ P.20-21 FastLane™ Structures ~Standard~ Kinase Products For details of products, please see "PRODUCTS AND SERVICES" on page 1~3. Tyrosine Kinases Note: Please contact us for availability or further information. Information may be changed without notice. Expression Protein Kinase Tag Carna Product Name Catalog No. Construct Sequence Accession Number Tag Location System HIS ABL(ABL1) 08-001 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) ABL(ABL1) BTN BTN-ABL(ABL1) 08-401-20N Full-length 2-1130 NP_005148.2 N-terminal DYKDDDDK Insect (sf21) ABL(ABL1) [E255K] HIS ABL(ABL1)[E255K] 08-094 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) HIS ABL(ABL1)[T315I] 08-093 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) ABL(ABL1) [T315I] BTN BTN-ABL(ABL1)[T315I] 08-493-20N Full-length 2-1130 NP_005148.2 N-terminal DYKDDDDK Insect (sf21) ACK(TNK2) GST ACK(TNK2) 08-196 Catalytic domain
    [Show full text]
  • Supplementary Information
    Immune differentiation regulator p100 tunes NF-κB responses to TNF Budhaditya Chatterjee,1, 2* Payel Roy,1, # * Uday Aditya Sarkar,1 Yashika Ratra,1 Meenakshi Chawla,1 James Gomes,2 Soumen Basak1§ 1Systems Immunology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, India. 2Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, India. #Current address: La Jolla Institute for Allergy and Immunology, USA *These authors contributed equally to this work. §Corresponding author. Email: [email protected] Supplementary Information I. Supplementary Fig. S1 – Fig. S4 and corresponding figure legends II. Supplementary Tables III. Detailed description of global gene expression analyses IV. A description of the mathematical model and related parameterization V. Supplementary References 1 I. Supplementary Fig. S1 – Fig. S4 and corresponding figure legends a Theoretical IKK2 activity inputs b Theoretical IKK2 activity inputs of varying peak amplitude of varying durations 60 100 50 30 NEMO-IKK2(nM) 0 NEMO-IKK2 (nM) 0 simulated NF-κB activities simulated NF-κB activities 100 100 (nM) (nM) 50 50 Bn Bn κ κ NF NF 0 0 0 2 4 6 8 0 2 4 6 8 time (hr) time (hr) c experimentally-derived IKK2 activity inputs 100 TNFc TNFp 50 NEMO-IKK2 activity(nM) 0 0 2 4 6 8 0 2 4 6 8 time (hr) Figure S1: In silico studies of the NF-κB system: a) A library of twelve theoretical IKK2 activity profiles with an invariant signal duration of 8 hr and peak amplitude uniformly varying from 10 nM to 100 nM was used as model inputs (top) for simulating NF-κBn responses in a time course (bottom).
    [Show full text]
  • Proteome Profiler™ Human Phospho-MAPK Array
    Proteome Profiler™ Array Human Phospho-MAPK Array Kit Catalog Number ARY002 For the parallel determination of the relative levels of phosphorylation of Mitogen-Activated Protein Kinases (MAPKs) and other serine/threonine kinases. This package insert must be read in its entirety before using this product. FOR RESEARCH USE ONLY. NOT FOR USE IN DIAGNOSTIC PROCEDURES. TABLE OF CONTENTS Contents Page INTRODUCTION 2 PRINCIPLE OF THE ASSAY . 2 TECHNICAL HINTS AND LIMITATIONS 2 MATERIALS PROVIDED . 3 OTHER MATERIALS REQUIRED 3 SAMPLE PREPARATION . 4 REAGENT PREPARATION 4 ARRAY PROTOCOL. .5 DATA ANALYSIS 6 PROFILING KINASE PHOSPHORYLATION . 7 SPECIFICITY - COMPETITION 9 SPECIFICITY - PATHWAY INHIBITION . 10 APPENDIX 11 MANUFACTURED AND DISTRIBUTED BY: R&D Systems, Inc. TELEPHONE: (800) 343-7475 614 McKinley Place NE (612) 379-2956 Minneapolis, MN 55413 FAX: (612) 656-4400 United States of America E-MAIL: [email protected] DISTRIBUTED BY: R&D Systems Europe, Ltd. 19 Barton Lane TELEPHONE: +44 (0)1235 529449 Abingdon Science Park FAX: +44 (0)1235 533420 Abingdon, OX14 3NB E-MAIL: [email protected] United Kingdom R&D Systems China Co. Ltd. 24A1 Hua Min Empire Plaza TELEPHONE: +86 (21) 52380373 726 West Yan An Road FAX: +86 (21) 52371001 Shanghai PRC 200050 E-MAIL: [email protected] INTRODUCTION Analyzing the phosphorylation status of all three major families of mitogen-activated protein kinases (MAPKs), the extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1 - 3), and different p38 isoforms (a/b/d/g), is essential in understanding the roles these signaling molecules play in mechanisms underlying cell function and disease.
    [Show full text]
  • Table SI. Enriched Genes in the Upregulated Genes of the Recovery Group According to the GO Molecular Function Terms. A, Downreg
    Table SI. Enriched genes in the upregulated genes of the recovery group according to the GO Molecular Function terms. A, Downregulated genes Adjusted Total Molecular Rank P‑value genes (n) Function Genes 1 <0.001 266 GO:0019899 Raf1 Timp1 Tbc1d8 Ube2g2 Ube2z enzyme binding Lonrf3 Tbc1d15 Rnf144a Ube2g1 Shc3 Rgcc Rnf19a Ube2j2 Rnf138 Atg13 Cks1b Ube2j1 Rnf19b Trib1 Trib3 Abtb2 Rnf125 Cdc42ep3 Nploc4 Cdc42ep4 Cdc42ep2 Rab11fip5 Arih2 Brms1 Tmem189 Mef2d Hspb1 Cdk9 Ksr1 Tnfaip3 Net1 Rnf180 Fgr Bhlhe41 Irs2 Ppp1r15a Asb4 Trim72 Zfp36 Sfn Xpo6 Fap Sox9 Mapk7 Itga3 Tubb5 Daxx Klf4 Stat3 Gab2 Myo9b Cstb Hmox1 Por Bcl2l1 Plin5 Chp1 Ube2i Sash1 Sqstm1 Rxra Slpi Sdc4 Tnfaip1 Cd40 Slc12a4 Map2k3 Ywhah Ppp1r12a Cry1 Plek Egfr Tnip1 Npc1l1 Rock2 Map2k6 Per1 Nfkbia Bdkrb2 Prkch Hif1a Golga5 Ripk1 Map3k1 Glud1 Nufip1 Clu Spry2 Hcls1 Ifnar2 Tuba1b Cdkn1a Sik1 Tmem173 Map3k2 Tnf Riok3 Ptpn2 Cep192 Smad2 Fas Jak2 Ankrd1 Rela Rps6ka4 Ankrd2 Rabgef1 Prkar1b Nop58 Casp8 Cflar Hdac4 Sele Nek2 Optn Nek6 Lcn2 Stom Traf6 Spred1 Nop56 Src Ccnl1 Ptpn22 Il6ra Pip5k1a F3 Bcl10 3110043O21Rik Tnfrsf1b Slc2a1 Sfpq Rpa2 Errfi1 Mad2l2 Tbc1d14 Uchl1 Glmn Scarb2 Ulk1 Ung Rad18 Mef2a Ctsc Ipo5 Mvp Kctd13 Msn Eif4ebp1 Casp3 Smad1 Ubash3b Ets1 Tirap Smad3 Tgfbr2 Ptgs2 Prr5l Micall1 Cnppd1 Map2k4 Tnks1bp1 Ppp1r32 Prdm4 Midn Ibtk Rusc2 Fmnl2 Ptpn23 Sh3bp4 Nop14 Kdm1a Serpine1 Gch1 Inf2 Csf3 Snx10 Txnip Egr1 Ranbp9 Akap12 Rab3gap2 Ddx58 Bcor Rabggta Pik3r1 Pkp2 Usp22 Shc1 Ptpn11 Fzd5 Cxcr4 Plaur Bag5 Maml1 Camk2n2 Taf7 Ywhag Ezr Jun Camk2d Parp4 Nod2 Ptafr Hmga2 Zfp746 Ptk2b Flot1
    [Show full text]
  • Lanthascreen Eu Kinase Binding Assay for RPS6KA4 Overview
    LanthaScreen™ Eu Kinase Binding Version No.: Page 1 of 17 Assay Validation Packet 1 Optimization of a LanthaScreen™ Eu Kinase Binding Assay for RPS6KA4 LanthaScreen™ Eu Kinase Binding Assay for RPS6KA4 Overview This protocol describes how to perform a LanthaScreen™ Eu Kinase Bindng Assay designed to detect and characterize kinase inhibitors. Procedure 1 describes an experiment to optimize the concentration of tracer to use with a specific kinase target. Procedure 2 describes how to perform kinase inhibitor affinity (IC50) measurements, using either the concentration of tracer determined by the user following Procedure 1 or using the concentration determined experimentally by Invitrogen. The protocol is accompanied by representative data generated at Invitrogen for both procedures. LanthaScreen™ Eu Kinase Binding Assays are based on the binding and displacement of a proprietary, Alexa Fluor® 647- labeled, ATP-competitive kinase inhibitor scaffold (kinase tracer) to the kinase of interest (Figure 1). Tracers based on a variety of scaffolds have been developed in order to address a wide range of kinase targets. Binding of the tracer to the kinase is detected using a europium-labeled anti-tag antibody, which binds to the kinase of interest. Simultaneous binding of both the tracer and antibody to the kinase results in a high degree of FRET (fluorescence resonance energy transfer) from the europium (Eu) donor fluorophore to the Alexa Fluor® 647 acceptor fluorophore on the kinase tracer. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET. Because the kinase tracers are based on ATP-competitive kinase inhibitors, they are suitable for detection of any compounds that bind to the ATP site.
    [Show full text]