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  • 1
    Online-Ressource
    Online-Ressource
    Newark :John Wiley & Sons, Incorporated,
    Schlagwort(e): Antiparasitic agents. ; Electronic books.
    Materialart: Online-Ressource
    Seiten: 1 online resource (452 pages)
    Ausgabe: 1st ed.
    ISBN: 9783527675395
    Serie: Drug Discovery in Infectious Diseases Series
    Sprache: Englisch
    Anmerkung: Protein Phosphorylation in Parasites: Novel Targets for Antiparasitic Intervention -- Contents -- Foreword -- Preface -- List of Contributors -- Part One: Bioinformatics -- 1 Computational Analysis of Apicomplexan Kinomes -- Introduction -- Public Resources and Computational Methods for Annotating Apicomplexan Kinomes -- Apicomplexan Resources -- Computational Methods for Phylogenetic Analysis -- Current Classification of Apicomplexan Kinomes -- Classification of the PK Superfamily -- Overview of Apicomplexan Kinomes -- An Abridged Description of Apicomplexan PK Groups -- Integrative Approaches to the Therapeutic Targeting of Apicomplexan Kinases -- Integration of Sequence and Structural Data -- Integration of Functional and Phosphoproteomic Data -- Conclusions and Future Perspectives -- List of Abbreviations -- Acknowledgments -- References -- 2 Phosphatomes of Unicellular Eukaryotic Parasites -- Introduction -- Protein Ser/Thr Phosphatases (PSPs) -- Protein Tyr Phosphatases (PTPs) -- Kinetoplastids -- Phosphatome Composition -- Functions of Protein Phosphatases -- Apicomplexans -- Phosphatome Composition -- Functions of Protein Phosphatases -- Entamoeba histolytica -- Phosphatome Composition -- Functions of Protein Phosphatases in E. histolytica -- Trichomonas vaginalis -- Giardia lamblia -- Encephalitozoon cuniculi -- Conclusions -- References -- Part Two: Functional Analysis of Parasite Kinomes and Phosphatomes -- 3 Trypanosomatid Phosphoproteomics -- Introduction -- Phosphoproteomic Techniques -- Phosphoproteomics Workflow -- Caveats and Limitations -- Quantitative Phosphoproteomics -- Trypanosomatid Phosphoproteomic Studies -- Leishmania donovani Phosphoproteomics -- Trypanosoma brucei Phosphoproteomics -- Trypanosoma cruzi Phosphoproteomics -- Trends in the Trypanosome Phosphoproteomes -- Phosphoproteomics in Antiparasitic Drug Discovery. , Future Directions -- Elucidating Trypanosome Signaling Pathways -- Technological Advances -- Conclusions -- References -- 4 Trypanosomatid Cell Division Kinases -- Introduction -- Cell Division Cycles in Trypanosomatids -- Cyclin-Dependent Kinases -- CRK3 -- Other CRKs -- NDR Kinases -- Aurora Kinase, Polo-Like Kinase, and Tousled-Like Kinase -- Aurora Kinases -- Tousled-Like Kinases -- Polo-Like Kinases -- Phosphatidylinositol Kinases -- Conclusions -- Acknowledgments -- References -- 5 Kinetoplastid AGC Kinases -- Introduction -- 3-Phosphoinositide-Dependent Kinase-1 (PDK-1) -- Cyclic Nucleotide-Dependent Protein Kinases: Protein Kinase A (PKA), Protein Kinase G (PKG) -- Protein Kinase B (PKB/Akt/RAC) -- Zinc Finger Kinase (ZFK) -- NDR Kinases -- RSK Kinases -- PKC-Like Kinase Activity -- Conclusions -- References -- 6 Plasmodium eIF2α Kinases -- Introduction -- PfeIK1 -- PfeIK2 -- PfPK4 -- Concluding Remarks -- References -- 7 Protein Kinases of the Parasitic Protist Entamoeba histolytica -- Entamoeba histolytica and Amebiasis -- Pathogenesis: Role of Signaling Pathways -- The Kinome of E. histolytica -- Serine/Threonine Kinases -- Homologs of Calcium/Calmodulin-Dependent Protein Kinases -- CMGC Group -- Cyclin-Dependent Kinases (CDKs) -- Homologs of MAPKs of E. histolytica -- Casein Kinase and Glycogen Synthase Kinase -- p21-Activated Kinases (PAKs) -- AGC Group -- Tyrosine Kinases -- Receptor Kinases -- Unclassified Protein Kinases (UPKs) -- Phosphatases -- Concluding Remarks -- References -- 8 Protein Phosphatases in Trypanosome Growth and Development -- Introduction -- Trypanosomatids -- Protein Phosphatases -- Bioinformatic Analysis of the Trypanosomatid Genomes and Proteomes -- Experimentally Characterized Trypanosomatid Protein Phosphatases -- Serine/Threonine-Specific Phosphatases -- DxDxT/V Phosphatases. , Protein Tyrosine Phosphatases (PTPs) -- Regulation of Differentiation via a Unique Protein Phosphatase Signaling Pathway in T. brucei -- The Potential of Protein Phosphatases as Drug Targets in Kinetoplastid Parasites -- Conclusions -- References -- Part Three: Role of Host Cell Kinomes and Phosphatomes in Parasitic Infections -- 9 Hijacking of Host Cell Signaling by Theileria -- Introduction -- Theileria-Induced Resistance to Apoptosis -- Hijacking of IKK Signalosomes by Theileria -- Functional CK2 is Required for Maintaining Theileria-Induced Transformation -- Mitogen-Activated Protein Kinases (MAPKs): The Activation of JNK -- JAK2 Kinase -- A PKA-Dependent Survival Pathway -- Increased Proliferation -- Phosphatidylinositol-3-Kinase (PI3-K) -- Akt/PKB -- Src Family Kinase, Hck -- Increased Metastatic Potential -- Src Family Kinases -- Rho Kinase (ROCK) -- JNK Activation Contributes to Metastatic Potential -- Persisting Within a Dividing Cell -- Hijacking of Host Cell Plk1 -- Conclusions -- References -- 10 The Role of Host- and Parasite-Encoded Kinases in Toxoplasma-Host Interactions -- Introduction -- T. gondii Invasion -- Role of Host Kinases During Parasite Growth -- T. gondii Egress -- Bradyzoite Development -- Virulence -- Conclusions -- Acknowledgments -- References -- 11 Macrophage Kinases in Leishmaniasis -- Introduction -- Macrophages Express Receptors for Leishmania Ligands -- Modulation of Macrophage CD40 Signaling by Leishmania -- Extracellular Signal-Regulated Kinase-1/2 (ERK-1/2) is Crucial in L. major Infection -- Signaling Intermediates are the Kinetic Proofreaders of Receptor Signaling -- Phosphatases Regulate Kinase-Mediated Signaling in Leishmania- Infected Macrophages -- Architecture of the Kinase Network in Macrophages -- Conclusions -- References -- Part Four: Drug Discovery. , 12 Selective Inhibition of Parasite Protein Kinases -- Introduction -- Inhibition of Parasite Protein Kinases -- Interaction of Protein Kinases with ATP -- Different Mechanisms of Kinase Inhibition -- Process and Methods for Finding, Designing, and Characterizing Selective Antiparasitic Kinase Inhibitors -- Parasite Kinases as Drug Targets -- Progress in the Study of Parasite Kinases -- Parasite-Specific Protein Kinases -- Structural Parasitology -- Case Studies -- Case Study #1: Plasmodium Protein Kinase 5 (PfPK5) -- Case Study #2: and Cryptosporidium CDPK1 -- Case Study #3: Plasmodium CDPKs with Small Gatekeepers -- Case Study #4: Type 2 Inhibitors -- Conclusions -- References -- 13 Kinase Inhibitors Among Hits from Malaria Cellular Screens -- Protein and Lipid Kinase Inhibitors in TCAMS -- Kinase Inhibitor Chemical Scaffolds -- Comparison of Human and Malaria Druggable Kinomes -- Assigning Compounds to Specific Kinases -- Lipid Kinases -- Experimental Target Deconvolution for Phenotypic Hits -- Affinity Methods -- Biochemical and Microbiological Methods -- Metabolomics -- Genetics -- References -- 14 Calcium-Dependent Protein Kinases of Apicomplexan Parasites as Drug Targets -- Apicomplexa -- Drug Targets and Structure-Guided Drug Design -- Apicomplexa-Specific Drug Targets -- Apicomplexa Calcium-Dependent Protein Kinases -- Toxoplasma gondii Calcium-Dependent Protein Kinases -- Kinase Inhibitor Selectivity and Apicomplexan CDPK -- Kinase Inhibitors and the Gatekeeper Residue -- CDPKs from T. gondii, N. caninum, and C. parvum Contain Glycine at the Gatekeeper Position -- Pyrazolopyrimidine-Based TgCDPK1 Inhibitors and Drug Selectivity -- The Broader Relevance of CDPKs As a Drug Target -- Acknowledgments -- References -- 15 Protein Kinases as Suitable Targets for Combating Eimeria spp. -- Eimeria spp. the Causative Agent of Coccidiosis of Poultry. , cGMP-Dependent Protein Kinases -- PKG Inhibitors -- Cyclin-Dependent Kinases (CDK)s -- Cyclins -- Conclusions -- Acknowledgments -- References -- 16 Receptor Tyrosine Kinase Signaling and Drug Targeting in Schistosomes -- Schistosomiasis and Its Control -- Tyrosine Kinase Signaling Pathways -- Receptor Tyrosine Kinases and Signaling in S. mansoni -- SER -- SmIR-1 and SmIR-2 -- VKRs -- CTKs -- Tyrosine Kinase Drug Targeting in Schistosomes -- Conclusions -- References -- 17 Protein Kinases as Drug Targets in the Treatment of Alveolar Echinococcosis -- Introduction -- The E. multilocularis Life Cycle -- AE and Current Antiparasitic Chemotherapy -- In Vitro Cultivation Systems and Drug Screening -- Rationale for Targeting Protein Kinases -- Genomics, Transcriptomics, and the Echinococcus Kinome -- E. multilocularis Receptor Kinases -- Cellular Echinococcus Kinases as Drug Targets -- What Next? -- Conclusions -- Acknowledgments -- References -- 18 Collaborative Drug Design of Plasmodium Kinase Inhibitors -- Introduction -- Collaboration Pool and SAM Pilot Goals -- SAM Drug Design Pilot Activities -- Deployment of Service Infrastructure -- SAM Drug Design Storyboard -- Discussion and Conclusions -- References -- Index.
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  • 2
    ISSN: 1550-7408
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    ISSN: 1365-2958
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie , Medizin
    Notizen: The transmission of malaria parasites to the mosquito depends critically on the rapid initiation of sexual reproduction in response to triggers from the mosquito midgut environment. We here identify an essential function for an atypical mitogen-activated protein kinase of the rodent malaria parasite Plasmodium berghei, Pbmap-2, in male sexual differentiation and parasite transmission to the mosquito. A deletion mutant no longer expressing the Pbmap-2 protein develops as wild type throughout the asexual erythrocytic phase of the life cycle. Gametocytes, the sexual transmission stages, form normally and respond in vitro to the appropriate environmental cues by rounding up and emerging from their host cells. However, microgametocytes fail to release flagellated microgametes. Female development is not affected, as judged by the ability of macrogametes to become cross-fertilized by microgametes from a donor strain. Cellular differentiation of Pbmap-2 KO microgametocytes is blocked at a late stage of male gamete formation, after replication and mitoses have been completed and axonemes have been assembled. These data demonstrate a function for Pbmap-2 in initiating cytokinesis and axoneme motility, possibly downstream of a cell cycle checkpoint for the completion of replication and/or mitosis, which are extraordinarily rapid in the male gametocyte.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    ISSN: 1365-2958
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie , Medizin
    Notizen: Two members of the mitogen-activated protein kinase (MAPK) family have been previously characterized in Plasmodium falciparum, but in vitro attempts at identifying MAP kinase kinase (MAPKK) homologues have failed. Here we report the characterization of a novel plasmodial protein kinase, PfPK7, whose top scores in blastp analysis belong to the MAPKK3/6 subgroup of MAPKKs. However, homology to MAPKKs is restricted to regions of the C-terminal lobe of the kinase domain, whereas the N-terminal region is closer to fungal protein kinase A enzymes (PKA, members of the AGC group of protein kinases). Hence, PfPK7 is a ‘composite’ enzyme displaying regions of similarity to more than one protein kinase family, similar to a few other plasmodial protein kinases. PfPK7 is expressed in several developmental stages of the parasite, both in the mosquito vector and in the human host. Recombinant PfPK7 displayed kinase activity towards a variety of substrates, but was unable to phosphorylate the two P. falciparum MAPK homologues in vitro, and was insensitive to PKA and MEK inhibitors. Together with the absence of a typical MAPKK activation site in its T-loop, this suggests that PfPK7 is not a MAPKK orthologue, despite the fact that this enzyme is the most ‘MAPKK-like’ enzyme encoded in the P. falciparum genome. This is consistent with recent observations that the plasmodial MAPKs are not true orthologues of the ERK1/2, p38 or JNK MAPKs, and strengthens the evidence that classical three-component module-dependent MAPK signalling pathways do not operate in malaria parasites, a feature that has not been described in any other eukaryote.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Parasitology research 80 (1994), S. 255-258 
    ISSN: 1432-1955
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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