Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular stresses is mediated via SAPKK3 (MKK6); Comparison of the specificities of SAPK3 and SAPK2 (RK/p38)

Ana Cuenda, Philip Cohen, Valérie Buée-Scherrer, Michel Goedert

    Research output: Contribution to journalArticle

    306 Citations (Scopus)

    Abstract

    Stress-activated protein kinase-3 (SAPK3), a recently described MAP kinase family member with a widespread tissue distribution, was transfected into several mammalian cell lines and shown to be activated in response to cellular stresses, interleukin-1 (IL-1) and tumour necrosis factor (TNF) in a similar manner to SAPK1 (also termed JNK) and SAPK2 (also termed p38, RK, CSBP and Mxi2). SAPK3 and SAPK2 were activated at similar rates in vitro by SAPKK3 (also termed MKK6), and SAPKK3 was the only activator of SAPK3 that was induced when KB or 293 cells were exposed to cellular stresses or stimulated with IL-1 or TNF. Co-transfection with SAPKK3 induced SAPK3 activity and greatly enhanced activation in response to osmotic shock. These experiments indicate that SAPKK3 mediates the activation of SAPK3 in several mammalian cells. SAPK3 and SAPK2 phosphorylated a number of proteins at similar rates, including the transcription factors ATF2, Elk-1 and SAP1, but SAPK3 was far less effective than SAPK2 in activating MAPKAP kinase-2 and MAPKAP kinase-3. Unlike SAPK2, SAPK3 was not inhibited by the drug SE 203580. SAPK3 phosphorylated ATF2 at Thr69, Thr71 and Ser90, the same residues phosphorylated by SAPK1, whereas SAPK2 only phosphorylated Thr69 and Thr71. Our results suggest that cellular functions previously attributed to SAPK1 and/or SAPK2 may be mediated by SAPK3.

    Original languageEnglish
    Pages (from-to)295-305
    Number of pages11
    JournalEMBO Journal
    Volume16
    Issue number2
    DOIs
    Publication statusPublished - 15 Jan 1997

    Keywords

    • IL-1
    • MAP kinase kinase
    • MEK
    • Stress
    • TNF

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