Feedback control of the protein kinase TAK1 by SAPK2a/p38

Peter C. F. Cheung, David G. Campbell, Angel R. Nebreda, Philip Cohen

    Research output: Contribution to journalArticle

    206 Citations (Scopus)

    Abstract

    NOTE: THE MATHEMATICAL SYMBOLS/SPECIAL CHARACTERS IN THIS ABSTRACT CANNOT BE DISPLAYED CORRECTLY ON THIS PAGE. PLEASE REFER TO THE ABSTRACT IN THE PUBLISHER'S WEBSITE FOR AN ACCURATE DISPLAY. TAB1, a subunit of the kinase TAK1, was phosphorylated by SAPK2a/p38? at Ser423, Thr431 and Ser438 in vitro. TAB1 became phosphorylated at all three sites when cells were exposed to cellular stresses, or stimulated with tumour necrosis factor-? (TNF-?), interleukin-1 (IL-1) or lipopolysaccharide (LPS). The phosphorylation of Ser423 and Thr431 was prevented if cells were pre-incubated with SB 203580, while the phosphorylation of Ser438 was partially inhibited by PD 184352. Ser423 is the first residue phosphorylated by SAPK2a/p38? that is not followed by proline. The activation of TAK1 was enhanced by SB 203580 in LPS-stimulated macrophages, and by proinflammatory cytokines or osmotic shock in epithelial KB cells or embryonic fibroblasts. The activation of TAK1 by TNF-?, IL-1 or osmotic shock was also enhanced in embryonic fibroblasts from SAPK2a/p38-?deficient mice, while incubation of these cells with SB 203580 had no effect. Our results suggest that TAB1 participates in a SAPK2a/p38?-mediated feedback control of TAK1, which not only limits the activation of SAPK2a/p38? but synchronizes its activity with other signalling pathways that lie downstream of TAK1 (JNK and IKK).
    Original languageEnglish
    Pages (from-to)5793-5805
    Number of pages13
    JournalThe EMBO Journal
    Volume22
    Issue number21
    DOIs
    Publication statusPublished - 2003

    Fingerprint

    Mitogen-Activated Protein Kinase 14
    Protein Kinases
    Feedback control
    Phosphorylation
    Chemical activation
    Osmotic Pressure
    Fibroblasts
    Interleukin-1
    Lipopolysaccharides
    KB Cells
    Macrophages
    Proline
    Websites
    Phosphotransferases
    Tumor Necrosis Factor-alpha
    Epithelial Cells
    Display devices
    Cells
    Cytokines
    SB 203580

    Keywords

    • p38
    • SB 203580
    • Stress-activated protein kinase (SAPK)
    • TAB1
    • TAK1
    • SAPK

    Cite this

    Cheung, Peter C. F. ; Campbell, David G. ; Nebreda, Angel R. ; Cohen, Philip. / Feedback control of the protein kinase TAK1 by SAPK2a/p38. In: The EMBO Journal. 2003 ; Vol. 22, No. 21. pp. 5793-5805.
    @article{6fcab80c20994bfe937a04a07563b942,
    title = "Feedback control of the protein kinase TAK1 by SAPK2a/p38",
    abstract = "NOTE: THE MATHEMATICAL SYMBOLS/SPECIAL CHARACTERS IN THIS ABSTRACT CANNOT BE DISPLAYED CORRECTLY ON THIS PAGE. PLEASE REFER TO THE ABSTRACT IN THE PUBLISHER'S WEBSITE FOR AN ACCURATE DISPLAY. TAB1, a subunit of the kinase TAK1, was phosphorylated by SAPK2a/p38? at Ser423, Thr431 and Ser438 in vitro. TAB1 became phosphorylated at all three sites when cells were exposed to cellular stresses, or stimulated with tumour necrosis factor-? (TNF-?), interleukin-1 (IL-1) or lipopolysaccharide (LPS). The phosphorylation of Ser423 and Thr431 was prevented if cells were pre-incubated with SB 203580, while the phosphorylation of Ser438 was partially inhibited by PD 184352. Ser423 is the first residue phosphorylated by SAPK2a/p38? that is not followed by proline. The activation of TAK1 was enhanced by SB 203580 in LPS-stimulated macrophages, and by proinflammatory cytokines or osmotic shock in epithelial KB cells or embryonic fibroblasts. The activation of TAK1 by TNF-?, IL-1 or osmotic shock was also enhanced in embryonic fibroblasts from SAPK2a/p38-?deficient mice, while incubation of these cells with SB 203580 had no effect. Our results suggest that TAB1 participates in a SAPK2a/p38?-mediated feedback control of TAK1, which not only limits the activation of SAPK2a/p38? but synchronizes its activity with other signalling pathways that lie downstream of TAK1 (JNK and IKK).",
    keywords = "p38, SB 203580, Stress-activated protein kinase (SAPK), TAB1, TAK1, SAPK",
    author = "Cheung, {Peter C. F.} and Campbell, {David G.} and Nebreda, {Angel R.} and Philip Cohen",
    note = "dc.publisher: Nature Publishing Group",
    year = "2003",
    doi = "10.1093/emboj/cdg552",
    language = "English",
    volume = "22",
    pages = "5793--5805",
    journal = "EMBO Journal",
    issn = "0261-4189",
    publisher = "EMBO Press",
    number = "21",

    }

    Feedback control of the protein kinase TAK1 by SAPK2a/p38. / Cheung, Peter C. F.; Campbell, David G.; Nebreda, Angel R.; Cohen, Philip.

    In: The EMBO Journal, Vol. 22, No. 21, 2003, p. 5793-5805.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Feedback control of the protein kinase TAK1 by SAPK2a/p38

    AU - Cheung, Peter C. F.

    AU - Campbell, David G.

    AU - Nebreda, Angel R.

    AU - Cohen, Philip

    N1 - dc.publisher: Nature Publishing Group

    PY - 2003

    Y1 - 2003

    N2 - NOTE: THE MATHEMATICAL SYMBOLS/SPECIAL CHARACTERS IN THIS ABSTRACT CANNOT BE DISPLAYED CORRECTLY ON THIS PAGE. PLEASE REFER TO THE ABSTRACT IN THE PUBLISHER'S WEBSITE FOR AN ACCURATE DISPLAY. TAB1, a subunit of the kinase TAK1, was phosphorylated by SAPK2a/p38? at Ser423, Thr431 and Ser438 in vitro. TAB1 became phosphorylated at all three sites when cells were exposed to cellular stresses, or stimulated with tumour necrosis factor-? (TNF-?), interleukin-1 (IL-1) or lipopolysaccharide (LPS). The phosphorylation of Ser423 and Thr431 was prevented if cells were pre-incubated with SB 203580, while the phosphorylation of Ser438 was partially inhibited by PD 184352. Ser423 is the first residue phosphorylated by SAPK2a/p38? that is not followed by proline. The activation of TAK1 was enhanced by SB 203580 in LPS-stimulated macrophages, and by proinflammatory cytokines or osmotic shock in epithelial KB cells or embryonic fibroblasts. The activation of TAK1 by TNF-?, IL-1 or osmotic shock was also enhanced in embryonic fibroblasts from SAPK2a/p38-?deficient mice, while incubation of these cells with SB 203580 had no effect. Our results suggest that TAB1 participates in a SAPK2a/p38?-mediated feedback control of TAK1, which not only limits the activation of SAPK2a/p38? but synchronizes its activity with other signalling pathways that lie downstream of TAK1 (JNK and IKK).

    AB - NOTE: THE MATHEMATICAL SYMBOLS/SPECIAL CHARACTERS IN THIS ABSTRACT CANNOT BE DISPLAYED CORRECTLY ON THIS PAGE. PLEASE REFER TO THE ABSTRACT IN THE PUBLISHER'S WEBSITE FOR AN ACCURATE DISPLAY. TAB1, a subunit of the kinase TAK1, was phosphorylated by SAPK2a/p38? at Ser423, Thr431 and Ser438 in vitro. TAB1 became phosphorylated at all three sites when cells were exposed to cellular stresses, or stimulated with tumour necrosis factor-? (TNF-?), interleukin-1 (IL-1) or lipopolysaccharide (LPS). The phosphorylation of Ser423 and Thr431 was prevented if cells were pre-incubated with SB 203580, while the phosphorylation of Ser438 was partially inhibited by PD 184352. Ser423 is the first residue phosphorylated by SAPK2a/p38? that is not followed by proline. The activation of TAK1 was enhanced by SB 203580 in LPS-stimulated macrophages, and by proinflammatory cytokines or osmotic shock in epithelial KB cells or embryonic fibroblasts. The activation of TAK1 by TNF-?, IL-1 or osmotic shock was also enhanced in embryonic fibroblasts from SAPK2a/p38-?deficient mice, while incubation of these cells with SB 203580 had no effect. Our results suggest that TAB1 participates in a SAPK2a/p38?-mediated feedback control of TAK1, which not only limits the activation of SAPK2a/p38? but synchronizes its activity with other signalling pathways that lie downstream of TAK1 (JNK and IKK).

    KW - p38

    KW - SB 203580

    KW - Stress-activated protein kinase (SAPK)

    KW - TAB1

    KW - TAK1

    KW - SAPK

    U2 - 10.1093/emboj/cdg552

    DO - 10.1093/emboj/cdg552

    M3 - Article

    VL - 22

    SP - 5793

    EP - 5805

    JO - EMBO Journal

    JF - EMBO Journal

    SN - 0261-4189

    IS - 21

    ER -