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LESTAURTINIB MIDOSTAURIN AXITINIB Tyrosine-protein kinase TIE-2 Serine/threonine-protein kinase 2Mitogen-activated protein kinase kinase kinase kinase 5 Serine/threonine-protein kinase MST2 NERATINIB SPS1/STE20-related protein kinase YSK4 SORAFENIB Dual specificity mitogen-activated protein kinase kinase 5 Proto-oncogene tyrosine-protein kinase MER Platelet-derivedTANDUTINIB growth factor receptor beta Epithelial discoidin domain-containing receptor 1 NINTEDANIB Mixed lineage kinase 7 Macrophage colonyTyrosine-protein stimulating kinasefactor receptorreceptor UFOTyrosine-protein kinase BLK Tyrosine-protein kinase LCK NILOTINIB Serine/threonine-protein kinase 10 NT-3 growth factor receptor DiscoidinMitogen-activated domain-containing protein receptor kinase 2 kinase kinase kinase 3 Tyrosine-protein kinase ABL Nerve growth factor receptor Trk-A FORETINIBEphrin type-B receptor 6 Adaptor-associated kinaseQUIZARTINIB Ephrin type-AEphrin receptor type-B receptor5 2 Mitogen-activated proteinTyrosine-protein kinase kinase kinaseTyrosine-protein kinase JAK3 kinase 2 kinase receptor FLT3 Fibroblast growth factorSerine/threonine-protein receptor 1 kinase Aurora-B Ephrin type-A receptor 8 Serine/threonine-proteinDual specificty protein kinase kinase PLK4Mitogen-activated CLK1 protein kinase kinase kinase 12 Misshapen-like kinase 1Cyclin-dependent kinase-like 2 Platelet-derivedLINIFANIB growth factor receptorEphrin alpha type-A receptor 4 c-Jun N-terminal kinaseALISERTIB 3 Serine/threonine-protein kinase SIK1 PONATINIB Dual specificity protein kinaseStem TTK cell growthHomeodomain-interacting factor receptorTyrosine-proteinTyrosine proteinkinase kinase non-receptorkinase TYK2 4 protein 2 Maternal embryonic leucine zipper kinase Tyrosine-protein kinase ABL2NUAK family SNF1-like kinase 2 Interleukin-1 receptor-associatedSerine/threonine-proteinVascular kinase endothelial 1 Neurotrophic kinasegrowth Aurora-A factortyrosine receptor kinase receptor2 type 2 Ephrin type-B receptor 3 Serine/threonine-protein kinaseTyrosine-protein SRPK1 kinaseMitogen-activated YES protein kinase kinase kinase kinase 1 Tyrosine-proteinGILTERITINIB kinase receptorBcr/AblTyrosine-protein RETfusion protein kinase TXK Non-receptor tyrosine-protein kinase TNK1 Mitogen-activated protein kinase kinase kinase 4 ILORASERTIBALECTINIBCABOZANTINIBTRAF2-OSI-930 and NCK-interacting kinase Fibroblast growth factorMAPSerine/threonine-protein receptor kinase p383 alpha AFATINIB kinase MST1 Tyrosine-protein kinaseMitogen-activated ITK/TSK protein kinase kinase kinaseSerine/threonine-protein 2 kinase 25 HepatocyteProto-oncogene growthENTOSPLETINIB factor receptor tyrosine-proteinCell division kinase protein ROS kinase 8 G protein-coupledBone morphogeneticSerine/threonine-protein receptor protein kinase receptor 4 Casein type-2 kinase kinase MST4 II alpha (prime) c-Jun N-terminal kinaseDual specificity 1 proteinDual kinase specificity CLK3 mitogen-activatedReceptorCasein protein kinase tyrosine-proteinkinase I epsilon kinase 2 kinase erbB-3 ALK tyrosineSerine/threonine-protein kinase receptor kinase RAF MAP kinaseHomeodomain-interacting signal-integrating kinase 2 protein kinaseTyrosine-protein 2 kinase SYKBRIVANIB DASATINIB Tyrosine-protein kinase Lyn Receptor protein-tyrosine kinaseSerine/threonine-protein erbB-4 kinase pknB DACTOLISIBReceptor protein-tyrosineBMP-2-inducible kinase erbB-2 protein kinase Dual specificity mitogen-activatedTRAMETINIBSerine/threonine-protein protein kinase kinase kinase 1 MRCKTyrosine-protein beta Receptor-interactingkinase Srms serine/threonine-protein kinase 1 Tyrosine-protein kinaseTyrosine-proteinFibroblast FRK growthVascular kinase factor FGR endothelialVascular receptor growthendothelial 2 factor growth receptor factor 3 receptor 1 Myosin light chainBone kinase morphogenetic protein receptor type-1B Cyclin-dependent kinase 7 c-Jun N-terminal kinase 2 VascularCOBIMETINIB Serine/threonine-proteinendothelial growth factor kinase receptorSerine/threonine-protein 16 kinase 32B Serine/threonine-proteinProtein kinase kinase N2 Chk1 EphrinSerine/threonine-proteinInterferon-induced- type-A receptor double-stranded 6 kinase TAO3 RNA-activated protein kinase ALVOCIDIB Serine/threonine-proteinSerine/threonine-protein kinase SRPK3 kinase RIO1 RibosomalTyrosine-protein protein S6 kinase kinaseIBRUTINIB alpha 3SRC TIVOZANIB Tyrosine-proteinActivin kinase receptor FES type-1 Serine/threonine-protein kinase RIO3 SIROLIMUS SEMAXANIB Dual-specificityFEDRATINIB tyrosine-phosphorylationLIM domain regulated kinase 1 kinase 1A Tyrosine-protein kinase receptor Tie-1 TRABECTEDIN Mitogen-activated protein kinase kinase kinase 3 Macrophage-stimulatingTyrosine-protein protein receptor kinase BTK Serine/threonine-proteinMammalianFocal adhesion target kinase of kinaseRapamycin GAK 1 (mTORC1)myosinInsulin light receptor-relatedchain kinaseEphrin 2 proteintype-B receptor 4 Dual specificity proteinCDK3/cyclin kinase CLK4 ELeucine-rich repeat serine/threonine-protein kinase 2 Calcium-dependent proteinActivin kinase receptor 1 type-2B Serine/threonine-proteinSerine/threonine-protein kinase ULK2Serine/threonine-protein kinase PCTAIRE-1Tyrosine-protein kinase kinase NEK2 JAK2 Tyrosine-protein kinase BMX Cyclin-dependentOMIPALISIB kinase 4/cyclin D1 Myosin IIIA CaM-kinase kinase beta Serine/threonine-protein kinaseU4/U6 PAK small Tankyrase-24 nuclear ribonucleoproteinMitogen-activatedTyrosine-protein Prp4 proteinCitronkinase Rho-interactingkinaseCTK kinase kinase kinase 13 Dual specificityMAP/microtubule tyrosine-phosphorylation-regulated affinity-regulating kinase kinase 2 1B cGMP-dependent protein kinaseSerine/threonine-protein 1 betaSerine/threonine-protein kinaseAMP-activated kinaseRho-associated PIM2 Aurora-C Cyclin-dependentproteinCyclin-dependent protein kinase- kinase alpha-1 kinase1kinaseCaM subunit 2 1/cyclin kinase B1I gamma Serine/threonine-proteinSerine/threonine-protein kinase kinase 24 PCTAIRE-3 cAMP-dependent protein kinase alpha-catalytic subunit Serine/threonine-protein kinase 17B Eukaryotic translation initiation factor 2-alpha kinase 4 Serine/threonine-proteinCasein kinase kinase Sgk1 Dual-specificityII Casein kinase tyrosine-phosphorylation I alphaTGF-beta receptor regulated type II kinaseSerine/threonine-protein 3 Dual specificity mitogen-activatedCasein kinase kinase PFTAIRE-1 I isoformprotein kinasealpha-like kinase 3 Ribosomal proteinSerine/threonine-proteinCaM S6 kinase kinase alpha II gamma 5 kinase 17ACyclin-dependentDANUSERTIBEpidermal growth kinase factor 9 receptor Hormonally up-regulated neu tumor-associated kinase Casein kinase I gamma 1 Receptor-typeProtein tyrosine-proteindelta homologSerine/threonine-protein 1 kinaseMitogen-activated FLT3 Interleukin-1 protein kinase kinase PRP4 receptor-associated kinasehomolog kinase 10 kinase 3 Phosphorylase kinase gammaTyrosine-protein subunitCyclin-dependent 2 Cyclin-dependent kinaseGCaM protein-coupled kinaseCSK kinase II alpha5 kinase receptor 7/ cyclin kinaseMAP H kinase 5 p38 Myosin light chain kinase- smooth muscle Inhibitor of nuclear factor kappa B kinase betaCyclin-dependent subunit kinaseEukaryotic 2/cyclinSerine/threonine-proteinDual A translationspecificity mitogen-activatedinitation factorkinaseEphrin WNK2 protein type-A kinase receptor kinase; 3 MEK1/2Phosphatidylinositol-4-phosphate 5-kinase type-1 alpha Serine/threonine-proteinInhibitor kinase of nuclear RIPK2 factorG protein-coupled kappa B kinase receptor epsilonMyelin kinase subunit transcription 6MASITINIB factor 1 Myotonin-protein kinase MAP kinase p38 gamma Testis-specificSerine/threonine-proteinDual-specificity serine/threonine-proteinProgrammed tyrosine-phosphorylation cell kinase death proteinEEF2Kkinase 42 regulated kinase 2 Cyclin-dependent kinase 4 Casein kinase I isoform gamma-3PD-0325901 CaM kinaseProtein I delta kinaseCyclin-dependent C alpha kinase 5/CDK5 activatorSerine/threonine-protein 1 kinase 36 Tyrosine-protein kinaseAMP-activated JAK1 INGENOL protein MEBUTATE kinase (AMPK)Cyclin-dependentcAMP-dependent alpha-1/beta-1/gamma-1 proteinkinase 13kinase (PKA) Chaperone activity of bc1 complex-like- mitochondrial Protein kinaseProtein C thetaProtein kinase kinase C delta C gamma Ephrin type-A receptorTyrosine-protein 2 kinase TEC Mitogen-activated protein kinase 4 CaM kinase I alphaSerine/threonine-proteinInhibitor of nuclear kinase factor PRKX kappa B kinase alpha subunit Mitogen-activated protein kinase kinase kinase 9 Protein kinase C zeta Muscle- skeletal receptorProtein tyrosine kinase protein C (PKC) kinase Tubulin alpha-1Serine/threonine-protein chain kinase PFTAIRE-2 Glycogen synthaseMAP kinase-3 kinase betap38 deltaTyrosine-proteinPhosphorylase kinaseDeath-associated FERkinase gamma protein subunit kinase 1 3 Receptor-interacting serine/threonine-protein kinase 4 Serine/threonine-proteinInsulin-like growth kinaseGlycogen factorTBK1 synthase I receptorMAP kinase-3 kinase-interactingProteinCaM alpha kinase kinaseULK3 II C serine/threonine-proteinkinasebeta kinase MNK1 Serine/threonine-protein kinase TNNI3K Serine/threonine-protein kinase PAK7 LINSITINIB MAP/microtubule affinity-regulating kinase 4 Protein kinase N1 DualSerine/threonine-protein specificity protein kinase kinase CLK2 PIM1 Eukaryotic translationAnkyrin repeat initiation and factor protein 2-alpha kinase kinase domain-containing 1 protein 1 MAP Tyrosine-proteinkinase p38 beta kinase receptorInsulin TYRO3INSULIN receptor HUMAN Serine/threonine-protein kinase PAK 2 Serine/threonine-protein kinase Nek1 3-phosphoinositide dependent proteinProtein kinase-1
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  • The Legionella Kinase Legk7 Exploits the Hippo Pathway Scaffold Protein MOB1A for Allostery and Substrate Phosphorylation

    The Legionella Kinase Legk7 Exploits the Hippo Pathway Scaffold Protein MOB1A for Allostery and Substrate Phosphorylation

    The Legionella kinase LegK7 exploits the Hippo pathway scaffold protein MOB1A for allostery and substrate phosphorylation Pei-Chung Leea,b,1, Ksenia Beyrakhovac,1, Caishuang Xuc, Michal T. Bonieckic, Mitchell H. Leea, Chisom J. Onub, Andrey M. Grishinc, Matthias P. Machnera,2, and Miroslaw Cyglerc,2 aDivision of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892; bDepartment of Biological Sciences, College of Liberal Arts and Sciences, Wayne State University, Detroit, MI 48202; and cDepartment of Biochemistry, University of Saskatchewan, Saskatoon, SK S7N5E5, Canada Edited by Ralph R. Isberg, Tufts University School of Medicine, Boston, MA, and approved May 1, 2020 (received for review January 12, 2020) During infection, the bacterial pathogen Legionella pneumophila Active LATS1/2 phosphorylate the cotranscriptional regulator manipulates a variety of host cell signaling pathways, including YAP1 (yes-associated protein 1) and its homolog TAZ (tran- the Hippo pathway which controls cell proliferation and differen- scriptional coactivator with PDZ-binding motif). Phosphorylated tiation in eukaryotes. Our previous studies revealed that L. pneu- YAP1 and TAZ are prevented from entering the nucleus by being mophila encodes the effector kinase LegK7 which phosphorylates either sequestered in the cytosol through binding to 14-3-3 pro- MOB1A, a highly conserved scaffold protein of the Hippo path- teins or targeted for proteolytic degradation (6, 8). Consequently, way. Here, we show that MOB1A, in addition to being a substrate the main outcome of signal transduction along the Hippo pathway of LegK7, also functions as an allosteric activator of its kinase is changes in gene expression (6).