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PRPF4B PRPF4B RET MAP2K1 CDK3 MAPK1 SRC ABL1 CDK2 PTK2 WEE1 LYN CDK1 MAPK3 JAK2 TTK MAPK1 DYRK1B MAP2K1 EGFR PTK2 DYRK1A PKMYT1 ERBB2 MAPK3 MAPK14 ERBB2 FGR TNK2 YES1 BMX KDR DYRK1B SRC MET MAP2K2 DYRK1A FYN PTK2 YES1 MAPK14 MAPK9 FGR INSR YES1 LCK MAPK3 MAP2K3 FYN INSR MAP2K2 MAPK3 PEAK1 IGF1R ABL1 MAP2K6 SRC HIPK2 MAP2K4 FYN SYK HIPK1 MAP2K6 KIT MAPK9 GSK3B MAP3K6 ITK LCK SKMel28.Replicate.1 GSK3A SKMel28.Replicate.1 MAP3K5 SKMel28.Replicate.1 SRMS SKMel28.Replicate.1 AXL Kinome DYRK4 ActLoop CDK5 PSP MET NWK CDK16 DYRK2 ALK MAP2K4 0 10 20 30 40 50 0 10 20 30 40 50 0 20 40 60 80 100 0 10 20 30 40 50 60 70 Not in PSP/NWK INKA SKMel28.Replicate.1 PEAK1 1 MAPK3 ● 36 AXL SRC ● DYRK4 PTK2 ● CDK17 0.9 33 HIPK3 0.8 29 0.7 25 0.6 22 Score 0.5 18 YES1 ● JAK2 ● FYN ● Relative Score Relative 0.4 15 ● INSR ● MAPK14 LYN ● 0.3 11 MAPK1 ● LCK ●IGF1R ● 0.2 ● HIPK2 FGR ● 7 CDK1 CDK5 ● GSK3A ● GSK3B TYK2 ● 0.1 TNK2 ● EPHA2 ● FER ● 4 SYK ● ● HCK ● ALPK3 MAPK10 ● EPHA3 ABL2 ● AKT1 0 2 4 6 Kinase−CentricAKT2 ● AKT3 Equal Substrate−CentricABL1 ● ADRBK1 EvidenceARAF Only Contribution EvidenceALK Only Kinase−Centric Counts InKA Score SKMel28.Replicate.1 MAPK3 SRC PTK2 YES1 JAK2 FYN INSR MAPK14 LYN MAPK1 LCK IGF1R FGR CDK1 CDK5 GSK3A GSK3B HIPK2 TYK2 EPHA2 0 5 10 15 20 25 30 35 SKMel28.Replicate.1 FYN LCK CAV1 TYK2 IGF1R ITK GSK3A TEC YES1 STAT3 GSK3B PEAK1 CDK2 INSR VCL JAK2 MAP2K4 MAP2K1 PKMYT1 LYN TTK MAPK1 PTPRA MAP3K5 MAP3K6 MAPK3 WEE1 PRKACA MPZL1 MAPK14 MAP2K6 CDK1 RET HIPK2 MAP2K2 SRC PDGFRB PXN PDGFRA ABL1 MAP2K3 MET BMX EGFR FGR ERBB2 KDR PTK2 CDK5 CDK3 PRPF4B WEE1 ABL1 CDK2 MAPK1 SRC MAP2K1 CDK1 GSK3B RET LYN PRPF4B GSK3A MAP2K1 TTK MAPK1 PTK2 JAK2 EGFR PTK2 MAPK3 PKMYT1 ERBB2 GSK3B DYRK1B ERBB2 FGR GSK3A DYRK1A BMX MAP2K2 MAPK3 MAPK14 MET KDR DYRK1B HIPK2 PTK2 INSR DYRK1A HIPK1 GSK3B YES1 MAPK14 YES1 GSK3A MAP2K3 YES1 SRC MAPK3 FYN FYN LCK MAP2K2 MAPK3 TNK2 FYN FGR KIT HIPK2 INSR ABL1 MAP2K6 HIPK1 IGF1R MAP2K6 SRMS PEAK1 SKMel28.Replicate.2 DYRK4 SKMel28.Replicate.2 MAP2K4 SKMel28.Replicate.2 ITK SKMel28.Replicate.2 LCK Kinome DYRK2 ActLoop ALK PSP MET NWK AXL AXL CDK5 PDGFRA 0 10 20 30 40 50 0 10 20 30 40 50 0 20 40 60 80 100 0 20 40 60 Not in PSP/NWK INKA SKMel28.Replicate.2 AXL 1 SRC ● 33 DYRK4 PEAK1 ● CDK17 0.9 MAPK3 30 HIPK3 0.8 26 GSK3APTK2 ●● GSK3B 0.7 23 0.6 20 Score 0.5 16 ● Relative Score Relative YES1FYN● 0.4 MAPK1 ● INSR ● 13 ● MAPK14 JAK2 ● 0.3 LCK ● 10 HIPK2 ● IGF1R ● LYN ● 0.2 CDK5 ● FGR ● 7 EPHA2 ● TYK2 ● 0.1 3 ABL2 ● AKT2 EPHA3MAPK10● ● BCR−ABL 0 2 4 6 ADRBK1Kinase−Centric● AKT1 Equal Substrate−CentricABL1 ● ALK EvidenceAKT3 Only Contribution EvidenceBMX Only Kinase−Centric Counts InKA Score SKMel28.Replicate.2 SRC MAPK3 PTK2 GSK3A GSK3B FYN YES1 INSR MAPK1 MAPK14 JAK2 LCK HIPK2 IGF1R LYN FGR CDK5 EPHA2 TYK2 ABL2 0 5 10 15 20 25 30 SKMel28.Replicate.2 GSK3A PEAK1 LCK LYN CDK2 PDGFRB CDK1 TYK2 ITK HIPK2 PRKACA IGF1R INSR PTPRA YES1 SRC PDGFRA FYN VCL KDR MAP2K4 EPHA2 EGFR MAP2K6 MAP3K6 BCAR1 MET MAP3K5 PTK2 MAP2K3 GSK3B MAPK14 SYK BMX MAP2K2 FGR ABL1 RET MAP2K1 MAPK3 ERBB2 STAT3 JAK2 PXN CDK5 MAPK1 ALK PTK2 SRC EGFR CDK1 MAPK14 RET ERBB2 CDK3 PRPF4B WEE1 MET CDK2 GSK3B MET INSR PTK2 GSK3A BMX ABL1 MAPK14 MAPK3 PKMYT1 LYN PRPF4B DYRK1B ERBB2 EPHA1 GSK3B DYRK1A PTK2 TTK GSK3A MAPK1 MAP2K1 MAP2K1 LYN YES1 ALK YES1 EPHA2 SRC FGR KDR MAPK3 LCK JAK2 FGR DYRK1B FYN EGFR FYN DYRK1A EPHA2 ABL1 KIT TNK2 HIPK2 MAP2K4 EPHA2 PEAK1 HIPK1 INSR ITK MAPK1 LYN MAP3K6 MAP2K6 YES1 H2228.Replicate.1 HCK H2228.Replicate.1 MAP3K5 H2228.Replicate.1 MAP2K7 H2228.Replicate.1 FYN Kinome INSR ActLoop MAP2K6 PSP MAPK3 NWK AXL IGF1R MAP2K3 FLT1 0 10 20 30 40 50 60 0 5 10 15 20 25 30 35 0 50 100 150 200 0 50 100 150 Not in PSP/NWK INKA H2228.Replicate.1 PEAK1 1 PTK2 ● 58 AXL DYRK4 SRC ● HIPK3 0.9 52 CDK17 ALK ● 0.8 46 0.7 40 LYN ● 0.6 MET ● 35 EGFR ● MAPK3 EPHA2● ● Score 0.5 INSR ● 29 FYN ● ABL1 ● Relative Score Relative YES1 ● MAPK14 ●GSK3A ● GSK3B 0.4 23 0.3 17 LCK ● MAPK1 ● ABL2 ● ● 0.2 HCK ● IGF1R 12 JAK2FGR● ● CDK1CDK2 ● HIPK2 ● TYK2 ● 0.1 FGFR1 FERCDK5● ● 6 EPHA3 ● AURKA EPHA4 ● EPHB4 EPHB3 ● AKT2 MAPK10 ● TGFBR2SYK ● 0 2 4 6 8 10 ALPK3Kinase−Centric● ARAF Equal ADRBK1Substrate−Centric● AKT1 EvidenceAURKB Only Contribution EvidenceAKT3 Only Kinase−Centric Counts InKA Score H2228.Replicate.1 PTK2 SRC ALK LYN MET EGFR EPHA2 MAPK3 INSR ABL1 FYN YES1 MAPK14 GSK3A GSK3B LCK MAPK1 ABL2 IGF1R HCK 0 10 20 30 40 50 H2228.Replicate.1 MAP3K5 MAP2K2 MAP2K3 DOCK4 JAK2 MAP2K6 GSK3A MAP2K1 EPHA2 GSK3B MAP2K4 MAPK3 MAPK14 TEC CDK2 MAPK1 MAP3K6 EPHA1 ITGB1 PEAK1 GAB2 EML4 PXN ABI1 RET INPPL1 ALK CTNNA1 VASP GPRC5A KDR HCK ABL2 LYN MST1R STAT3 FGR PTPN11 MAP2K7 CRK ABL1 BMX NCK1 EGFR KIT ITGB4 PRKCE INPP5D PTK2 MET CDK1 CTNNA2 MPZL1 BCAR1 ACTN1 ERBB2 TNK2 CBL GAB1 CAV1 CTNND1 VCL MUC1 CTTN LCK YES1 SHC1 PTPRE FYN SRC PAG1 INSR ITK IRS1 PTPRA IGF1R PDGFRA CD46 PDGFRB G6PD PIK3R1 NAMPT HIPK2 SDCBP PFN1 IRS2 AP2B1 PIK3R3 PRKACA PTTG1IP PRPF4B PRPF4B SRC EGFR CDK1 PTK2 WEE1 MET ALK MAPK14 RET ERBB2 CDK3 GSK3B MET ABL1 CDK2 GSK3A PKMYT1 INSR PTK2 MAPK3 ERBB2 LYN MAPK14 MAPK1 ALK TTK LYN DYRK1B BMX EPHA1 GSK3B DYRK1A JAK2 YES1 GSK3A EPHA2 MAP2K1 MAP2K1 TNK2 YES1 ABL1 FGR MAPK3 SRC PTK2 FYN MAPK1 LYN EGFR KDR DYRK1B LCK FGR KIT DYRK1A HIPK2 MAP2K4 ITK YES1 HIPK1 FYN TEC FYN HCK MAP3K5 MAPK3 EPHA2 H2228.Replicate.2 FYN H2228.Replicate.2 MAP2K6 H2228.Replicate.2 EPHA2 H2228.Replicate.2 HCK Kinome ABL2 ActLoop MAP2K3 PSP TYK2 NWK EGFR ABL1 INSR MAP2K7 0 10 20 30 40 50 0 10 20 30 40 50 0 50 100 150 200 0 50 100 150 Not in PSP/NWK INKA H2228.Replicate.2 PEAK1 1 SRC ● 50 AXL DYRK4 ALK ● PTK2 ● HIPK3 0.9 45 CDK17 ● 0.8 LYN 40 ● 0.7 EGFRMET ● 35 0.6 ABL1 ● 30 ● YES1FYN ● MAPK3 ● Score 0.5 25 GSK3A ● GSK3B Relative Score Relative MAPK14 ● EPHA2 ● 0.4 20 0.3 INSR ● 15 MAPK1 ● HCK ● LCK ERBB2 ● ABL2 ● JAK2 ● 0.2 CDK1CDK2 ● 10 ● HIPK2 TYK2 ●FGR ● EPHB4 ● CDK5 ● 0.1 EPHB3 ● IGF1R ● 5 TNK2 ● ERBB4 ● AURKA AKT2 FRK ● 0 1 2 3 4 5 ALPK3Kinase−Centric● ARAF Equal ADRBK1Substrate−Centric● AKT1 EvidenceAURKB Only Contribution EvidenceAKT3 Only Kinase−Centric Counts InKA Score H2228.Replicate.2 SRC ALK PTK2 LYN EGFR MET ABL1 FYN YES1 MAPK3 GSK3A GSK3B EPHA2 MAPK14 INSR HCK LCK MAPK1 ERBB2 ABL2 0 10 20 30 40 H2228.Replicate.2 PIK3R3 IRS1 PIK3R1 KIT ITGB1 NAMPT TEC NCK1 IRS2 CDK2 ABL2 MAP2K1 ITK INSR JAK2 GSK3B LYN HCK LCK FYN PTPRA MAPK3 ABL1 PXN INPP5D MAP2K2 PAG1 BCAR1 MAP2K3 MPZL1 MAPK1 PDGFRB GAB2 FGR CTNND1 CAV1 MAPK14 MAP3K6 PTTG1IP GAB1 RET HIPK2 INPPL1 CDK1 EPHA2 MAP3K5 G6PD SRC PRKACA MET MAP2K4 CTTN BMX MST1R ADRBK1 PTK2 PDGFRA EGFR MAP2K6 AP2B1 SHC1 MUC1 CBL PRKCE ITGB4 SDCBP GSK3A CD46 CAMK2A EML4 ERBB2 KDR PTPN11 GPRC5A EPHA1 YES1 TNK2 STAT3 VCL ALK HSP90AA1 TNS3 VIM ACTN1 ARHGAP35 HSP90AA2P MAP2K7 PTPRE BCR PRPF4B SRC ABL1 ABL1 MAPK1 WEE1 MET CDK1 ABL1 LYN ABL2 CDK3 ABL2 FYN LYN CDK2 MAPK14 HCK BTK PRPF4B DYRK1B ABL1 TTK ABL2 DYRK1A PKMYT1 EGFR MAPK1 MAPK3 ERBB2 KIT MAPK14 GSK3B BCR−ABL NTRK1 PEAK1 GSK3A RET MAP2K1 LYN YES1 JAK2 ERBB2 DYRK1B SRC MAP2K1 TYK2 DYRK1A FYN LCK PDGFRB MAPK3 HIPK2 MET TEC BTK HIPK1 SYK FLT1 TNK2 LYN ABL2 ITK GSK3B LCK ALK INSR GSK3A K562.Replicate.1 HCK K562.Replicate.1 MAPK3 K562.Replicate.1 MAPK1 K562.Replicate.1 YES1 Kinome DDR1 ActLoop MAP3K5 PSP YES1 NWK FYN HIPK3 MAP2K4 FGR 0 50 100 150 0 10 20 30 40 50 60 0 50 100 150 200 250 0 50 100 150 200 Not in PSP/NWK INKA K562.Replicate.1 PEAK1 1 ABL1 ● 273 DDR1 HIPK3 CDK17 0.9 245 DYRK4 AXL 0.8 218 FAM20B 0.7 191 0.6 164 Score 0.5 136 ABL2 ● Relative Score Relative 0.4 109 LYN ● 0.3 82 SRC ● MAPK1 ● FYN ● 0.2 BTK ● 55 MAPK3 ● HCK ● 0.1 YES1 ● LCK ● 27 GSK3A ● GSK3B JAK2 ● CDK1CDK2AKT3● ● TNK2 ● BCR−ABL MAPK14 HIPK2 ● SYK ● ●● PTK2 ● ● ●BMXTYK2FGRTEC● 0 5 10 15 20 ADRBK1Kinase−Centric● AKT2 EPHB4 ● MAPK10AURKAEqual● CDK5 PRKCB Substrate−CentricAKT1 ● ALK EvidenceALPK3 Only Contribution EvidenceBLK Only Kinase−Centric Counts InKA Score K562.Replicate.1 ABL1 ABL2 LYN SRC FYN MAPK1 BTK MAPK3 HCK YES1 LCK GSK3A GSK3B JAK2 TNK2 CDK1 CDK2 MAPK14 HIPK2 SYK 0 50 100 150 200 250 K562.Replicate.1 ARHGAP35 PRKACA CD46 YES1 ACTN1 CTTN GSK3A GAB1 PTPRA PTTG1IP G6PD MAP2K3 PFN1 MAP3K6 SHC1 MAP3K5 PTK2 PDGFRA HIPK2 ERBB2 SRC PKMYT1 MAPK14 MAP2K6 PDGFRB EGFR FGR STAT5B MPZL1 TTK MAP2K4 BMX WEE1 ABL2 CDK1 PRKCD NTRK1 HCK GSK3B CDK2 RET CRK TNK2 PEAK1 STAT5A ABL1 INPPL1 ABI1 KIT MAPK1 LYN DOK1 BCR JAK2 MAP2K1 NTRK2 WAS MAPK3 GAB2 NCK1 PLCG1 BTK SYK TEC FYN LCK MAP2K2 DOK2 FCGR2A FCGR2C FYB ITK CBL PIK3R2 SH2D2A BCR PRPF4B SRC ABL1 ABL1 ABL1 WEE1 MET CDK1 MAPK1 LYN ABL2 CDK3 ABL2 FYN LYN CDK2 MAPK14 HCK BTK PRPF4B MAPK3 ABL1 TTK ABL2 GSK3B PKMYT1 KIT MAPK1 GSK3A ERBB2 EGFR MAPK14 DYRK1B BCR−ABL NTRK1 LYN DYRK1A RET MAP2K1 BTK YES1 JAK2 ERBB2 MAPK3 SRC MAP2K1 TYK2 GSK3A FYN LCK ITK PEAK1 HIPK2 MET TEC GSK3B HIPK1 ABL2 FLT1 DYRK1B LYN ALK YES1 DYRK1A LCK SYK FGR YES1 K562.Replicate.2 HCK K562.Replicate.2 MAPK3 K562.Replicate.2 MAPK1 K562.Replicate.2 TNK2 Kinome PTK2 ActLoop EGFR PSP INSR NWK FYN DDR1 MAP2K4 PDGFRB 0 50 100 150 0 10 20 30 40 50 0 50 100 150 200 250 0 50 100 150 200 Not in PSP/NWK INKA K562.Replicate.2 PEAK1 1 ABL1 ● 269 DDR1 HIPK3 CDK17 0.9 242 DYRK4 AXL 0.8 215 TRIM28 0.7 188 0.6 161 Score 0.5 ABL2 ● 135 Relative Score Relative 0.4 108 LYN ● 0.3 81 FYNSRC● ● 0.2 MAPK1 ● BTK ● 54 MAPK3 ● HCK ● ● 0.1 ● YES1 ● 27 CDK1CDK2 GSK3AGSK3B ●● LCK JAK2 ● AKT3 ● TECTTKBCR−ABL● ● ● HIPK2● ●TNK2 SYKFGR ●●● MAPK14 ● PTK2 ● ● CDK5 ● ● TYK2 0 5 10 15 ADRBK1Kinase−CentricPRKCD● AKT2 MAPK10EPHB4 ● AURKAFEREqual● PRKCB Substrate−CentricAKT1 ● ALK EvidenceALPK3 Only Contribution EvidenceBLK Only Kinase−Centric Counts InKA Score K562.Replicate.2 ABL1 ABL2 LYN FYN SRC BTK MAPK1 HCK MAPK3 YES1 CDK1 CDK2 LCK GSK3A GSK3B JAK2
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  • Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse

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    Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only.
  • ITK Inhibitors for the Treatment of T-Cell Lymphoproliferative Disorders John C

    ITK Inhibitors for the Treatment of T-Cell Lymphoproliferative Disorders John C

    ITK Inhibitors for the Treatment of T-Cell Lymphoproliferative Disorders John C. Reneau, MD, PhD1, Steven R. Hwang, MD2, Carlos A. Murga-Zamalloa, MD1, Joseph J. Buggy, PhD3, James W. Janc, PhD3 and Ryan A. Wilcox, MD, PhD1 1University of Michigan, Ann Arbor, MI; 2Mayo Clinic, Rochester, MN; 3Corvus Pharmaceuticals, Inc., Burlingame, CA Introduction Results and Methods Conclusions • T-cell lymphomas (TCL) comprise a rare, aggressive, and Table 1: CPI-818 specifically inhibits ITK Figure 2: CPI-818 has minimal effect on normal T cells • CPI-818 is a potent ITK specific inhibitor, while CPI-893 inhibits both heterogeneous subtype of non-Hodgkin lymphoma B IC50 (nM) A ITK and RLK • Outcomes for patients with TCL remain poor and novel therapies are ITK RLK • Normal T cells express both ITK and RLK which can compensate for needed CPI-818 (ITKi) 2.3 260 inhibition of ITK function CPI-893 (ITK/RLKi) 0.36 0.4 • Engagement of the T-cell receptor (TCR) in malignant T-cells leads to • Malignant T cells almost exclusively express ITK, or express RLK at Kinome screening was performed for CPI-818 (ITKi) and CPI-893 (ITK/RLKi). CPI-818 (ITKi) had high interleukin-2-inudcible T-cell kinase (ITK) dependent activation of NF- specificity for ITK over RLK (IC50 2.3 nM and 260 nM, respectively). In contrast CPI-893 (ITK/RLKi) had a very low levels high affinity for both ITK and RLK (IC50 0.36 nM and 0.4 nM, respectively) 1 κB and GATA3, and promotes chemotherapy resistance . (A) Peripheral blood T cells from healthy donors were isolated by negative selection.
  • Redox-Mediated Regulation of the Tyrosine Kinase Zap70

    Redox-Mediated Regulation of the Tyrosine Kinase Zap70

    Redox-mediated regulation of the tyrosine kinase Zap70 DISSERTATION zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) genehmigt durch die Fakultät für Naturwissenschaften der Otto-von-Guericke-Universität von M.Sc. Christoph Thurm geb. am 27.06.1988 in Borna Gutachter: apl. Prof. Dr. Luca Simeoni PD Dr. rer. nat. Marcus Lettau eingereicht am: 02.02.2018 verteidigt am: 06.06.2018 Eigenständigkeitserklärung I. Eigenständigkeitserklärung Christoph Thurm Halberstädter Straße 29 39112 Magdeburg Hiermit erkläre ich, dass ich die von mir eingereichte Dissertation zu dem Thema Redox-mediated regulation of the tyrosine kinase Zap70 selbständig verfasst, nicht schon als Dissertation verwendet habe und die benutzten Hilfsmittel und Quellen vollständig angegeben wurden. Weiterhin erkläre ich, dass ich weder diese noch eine andere Arbeit zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) an anderen Einrichtungen eingereicht habe. Magdeburg, den 02.02.2018 ____________________________________ M.Sc. Christoph Thurm II ACKNOWLEDGEMENTS II. Acknowledgements Firstly, I would like to express my sincere gratitude to my supervisor Prof. Dr. Luca Simeoni. His extraordinary support during my PhD thesis together with his motivation and knowledge enabled me to pursue my dream. I could not have imagined having a better mentor. Furthermore, I would like to thank Prof. Dr. Burkhart Schraven for giving me the opportunity to work in his institute. His support, ideas, and the lively discussions promoted me to develop as a scientist. Special thanks go also to the whole AG Simeoni/Schraven - Ines, Camilla, Matthias, and Andreas - for the help with experiments, the discussions, and the fun we had. This helped to sustain also the longest days.
  • Map2k1 and Map2k2 Genes Contribute to the Normal Development of Syncytiotrophoblasts During Placentation

    Map2k1 and Map2k2 Genes Contribute to the Normal Development of Syncytiotrophoblasts During Placentation

    RESEARCH ARTICLE 1363 Development 136, 1363-1374 (2009) doi:10.1242/dev.031872 Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation Valérie Nadeau*, Stéphanie Guillemette*, Louis-François Bélanger, Olivier Jacob, Sophie Roy and Jean Charron† The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation. In the mouse, loss of Map2k1 function causes embryonic lethality, whereas Map2k2 mutants survive with a normal lifespan, suggesting that Map2k1 masks the phenotype due to the Map2k2 mutation. To uncover the specific function of MAP2K2 and the threshold requirement of MAP2K proteins during embryo formation, we have successively ablated the Map2k gene functions. We report here that Map2k2 haploinsufficiency affects the normal development of placenta in the absence of one Map2k1 allele. Most Map2k1+/–Map2k2+/– embryos die during gestation because of placenta defects restricted to extra-embryonic tissues. The impaired viability of Map2k1+/–Map2k2+/– embryos can be rescued when the Map2k1 deletion is restricted to the embryonic tissues. The severity of the placenta phenotype is dependent on the number of Map2k mutant alleles, the deletion of the Map2k1 allele being more deleterious. Moreover, the deletion of one or both Map2k2 alleles in the context of one null Map2k1 allele leads to the formation of multinucleated trophoblast giant (MTG) cells. Genetic experiments indicate that these structures are derived from Gcm1-expressing syncytiotrophoblasts (SynT), which are affected in their ability to form the uniform SynT layer II lining the maternal sinuses. Thus, even though Map2k1 plays a predominant role, these results enlighten the function of Map2k2 in placenta development.
  • Review Tec Kinases: a Family with Multiple Roles in Immunity

    Review Tec Kinases: a Family with Multiple Roles in Immunity

    Immunity, Vol. 12, 373±382, April, 2000, Copyright 2000 by Cell Press Tec Kinases: A Family Review with Multiple Roles in Immunity Wen-Chin Yang,*³§ Yves Collette,*³ inositol phosphates, but they are thought to be relevant Jacques A. NuneÁ s,*³ and Daniel Olive*² for binding of PtdIns lipids to the same sites. In most *INSERM U119 cases, PH domains bind preferentially to PtdIns (4,5)P2 Universite de la Me diterrane e and inositol (1,4,5) P3 (Ins (1,4,5) P3). However, the Btk 13009 Marseille PH domain binds PtdIns (3,4,5)P3 and Ins (1, 3, 4, 5)P4 France the tightest. PtdIns (3, 4, 5)P3, one of the products of the action of PI3K, is thought to act as a second messen- ger to recruit regulatory proteins to the plasma mem- brane via their PH domains (see below). Many of the Antigen receptors on T, B, and mast cells are multimo- mutations in Btk that lead to XLA are point mutations lecular complexes that are activated by interactions with that cluster at one end of the PH domain and could be external signals. These signals are then transmitted to predicted to impair binding to Ins (3,4,5)P (for review regulate gene expression and posttranscriptional modi- 3 see Satterthwaite et al., 1998a) (Figure 1b). Similarly, fications. Nonreceptor tyrosine kinases (NRTK) are key CBA/N xid mice carry an R28C mutation in the Btk PH players that relay and integrate these signals. NRTK are domain. The recent structure of the PH domain from divided into distinct families defined by a prototypic Btk complexed with Ins (1,3,4,5)P4 provides an explana- member: Src, Tec, Syk, Csk, Fes, Abl, Jak, Fak, Ack, tion for several mutations associated with XLA: mis- Brk, and Srm (Bolen and Brugge, 1997).