Use of a drug-resistant mutant of stress-activated protein kinase 2a/p38 to validate the in vivo specificity of SB 203580

Patrick A. Eyers, Paul Van Den Ijssel, Roy A. Quinlan, Michel Goedert, Philip Cohen (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    96 Citations (Scopus)

    Abstract

    Stress-activated protein kinase 2a, also called p38, is inhibited by SB 203580 and this drug has been used widely to implicate this enzyme in the regulation of many physiological processes. Here, we introduce a novel method of general application, which can be used to establish whether the effects of SB 203580 are mediated via inhibition of stress-activated protein kinase 2a/p38 or whether they result from 'non-specific' effects. Four events thought to occur upon activation of stress-activated protein kinase 2a/p38 have been established unequivocally. These are the activation of mitogen-activated protein kinase-activated protein kinase-2 and mitogen- and stress-activated protein kinase-1 and the phosphorylation of their presumed substrates, heat shock protein 27 and the transcription factor cyclic AMP response element binding protein, respectively. In contrast, the SB 203580-induced activation of c-Raf is independent of stress-activated protein kinase 2a/p38 inhibition. Copyright (C) 1999 Federation of European Biochemical Societies.

    Original languageEnglish
    Pages (from-to)191-196
    Number of pages6
    JournalFEBS Letters
    Volume451
    Issue number2
    DOIs
    Publication statusPublished - 21 May 1999

    Keywords

    • CREB
    • MAPKAP-K2
    • MSK1
    • p38
    • SAPK2
    • SB203580

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