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    Elimination of Protein Kinase MK5/PRAK Activity by Targeted Homologous Recombination (2003)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Shi, Yu
    Kotlyarov, Alexey
    Laabeta, Kathrin
    Gruber, Achim D (WE 12)
    Butt, Elke
    Marcus, Katrin
    Meyer, Helmut E
    Friedrich, Anke
    Volk, Hans-Dieter
    Gaestel, Matthias
    Quelle
    Molecular and Cellular Biology; 23(21) — S. 7732–7741
    ISSN: 0270-7306
    Sprache
    Englisch
    Verweise
    Pubmed: 14560018
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    MK5 (mitogen-activated protein kinase [MAPK]-activated protein kinase 5), also designated PRAK (p38-regulated and -activated kinase), was deleted from mice by homologous recombination. Although no MK5 full-length protein and kinase activity was detected in the MK5 knockout mice, the animals were viable and fertile and did not display abnormalities in tissue morphology or behavior. In addition, these mice did not show increased resistance to endotoxic shock or decreased lipopolysaccharide-induced cytokine production. Hence, MK5 deletion resulted in a phenotype very different from the complex inflammation-impaired phenotype of mice deficient in MK2, although MK2 and MK5 exhibit evolutional, structural, and apparent extensive functional similarities. To explain this discrepancy, we used wild-type cells and embryonic fibroblasts from both MK2 and MK5 knockout mice as controls to reexamine the mechanism of activation, the interaction with endogenous p38 MAPK, and the substrate specificity of both enzymes. In contrast to MK2, which shows interaction with and chaperoning properties for p38 MAPK and which is activated by extracellular stresses such as arsenite or sorbitol treatment, endogenous MK5 did not show these properties. Furthermore, endogenous MK5 is not able to phosphorylate Hsp27 in vitro and in vivo. We conclude that the differences between the phenotypes of MK5- and MK2-deficient mice result from clearly different functional properties of both enzymes.