26 research outputs found

    Expression of protein kinase C subspecies in human leukemia- lymphoma cell lines

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    AbstractExpression of protein kinase C (PKC) subspecies was studied in various human leukemia-lymphoma cell lines. The PKC in most cell lines examined was resolved into two major fractions corresponding to type II (β-sequence) and type III (α-sequence) PKC of the rat brain. The amounts of these two subspecies greatly varied among the cell lines. Type I PKC (γ-sequence) was expressed in none of the cell lines tested, but PKCs with undefined structures were frequently detected. The differential co-expression of several PKC subspecies is presumably related to the state of cell differentiation

    The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase

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    AbstractBackground: The p38 mitogen-activated protein (MAP) kinase regulates signal transduction in response to environmental stress. Pyridinylimidazole compounds are specific inhibitors of p38 MAP kinase that block the production of the cytokines interleukin-1 β and tumor necrosis factor α, and they are effective in animal models of arthritis, bone resorption and endotoxin shock. These compounds have been useful probes for studying the physiological functions of the p38-mediated MAP kinase pathway.Results: We report the crystal structure of a novel pyridinylimidazole compound complexed with p38 MAP kinase, and we demonstrate that this compound binds to the same site on the kinase as does ATP. Mutagenesis showed that a single residue difference between p38 MAP kinase and other MAP kinases is sufficient to confer selectivity among pyridinylimidazole compounds.Conclusions: Our results reveal how pyridinylimidazole compounds are potent and selective inhibitors of p38 MAP kinase but not other MAP kinases. It should now be possible to design other specific inhibitors of activated p38 MAP kinase using the structure of the nonphosphorylated enzyme

    Transcending Sovereignty: Locating Indigenous Peoples in Transboundary Water Law

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