SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1

Ana Cuenda, John Rouse, Yair N. Doza, Roger Meier, Philip Cohen (Lead / Corresponding author), Timothy F. Gallagher, Peter R. Young, John C. Lee

    Research output: Contribution to journalArticle

    1921 Citations (Scopus)

    Abstract

    A class of pyridinyl imidazoles inhibit the MAP kinase homologue, termed here reactivating kinase (RK) [Lee et al. (1994) Nature 372, 739–746]. We now show that one of these compounds (SB 203580) inhibits RK in vitro (IC50 = 0.6 ?M), suppresses the activation of MAPKAP kinase-2 and prevents the phosphorylation of heat shock protein (HSP) 27 in response to interleukin-1, cellular stresses and bacterial endotoxin in vivo. These results establish that MAPKAP kinase-2 is a physiological RK substrate, and that HSP27 is phosphorylated by MAPKAP kinase-2 in vivo. The specificity of SB 203580 was indicated by its failure to inhibit 12 other protein kinases in vitro, and by its lack of effect on the activation of RK kinase and other MAP kinase cascades in vivo. We suggest that SB 203580 will be useful for identifying other physiological roles and targets of RK and MAPKAP kinase-2.
    Original languageEnglish
    Pages (from-to)229-233
    Number of pages5
    JournalFEBS Letters
    Volume364
    Issue number2
    DOIs
    Publication statusPublished - 8 May 1995

    Keywords

    • MAP kinase
    • Protein kinase inhibitor
    • Cytokine
    • Osmotic stress
    • LPS
    • HSP27

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