Tumour necrosis factor-induced activation of c-Jun N-terminal kinase is sensitive to caspase-dependent modulation while activation of mitogen-activated protein kinase (MAPK) or p38 MAPK is not

Ahmed Mohamed, O. J. Jupp, H. M. Anderson, Alison Littlejohn, P. Vandenabeele, David Joseph MacEwan

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    The activation of the extracellular signal-regulated kinases (ERKs) by tumour necrosis factor-alpha (TNF) receptors (TNFRs) is an integral part of the cytokinc's pleiotropic cellular responses. Here we report differences in the caspase sensitivity and TNFR subtype activation of members of the ERK family. Inhibition in HeLa cells of caspase function by pharmacological inhibitors or the expression of CrmA (cytokine response modifier A), a viral modifier protein, blocks TNF-induced apoptosis or caspase-dependent protein kinase Cdelta and poly(ADP-ribose) polymerase protein degradation. TNFR1- or TNFR2-stimulated c-Jun N-terminal kinase (JNK) activity was attenuated in cells in which caspase activity was inhibited either by pharmacological blockers or CrmA expression. Both TNFR1- and TNFR2-stimulated JNK activity was caspase-sensitive; however, only TNFR1 was capable of stimulating p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK activities. TNFR1-stimulated p42/44 MAPK and p38 MAPK activities were insensitive to pharmacological caspase inhibition or CrmA. These findings were supported when measuring TNF-induced cytosolic phospholipase A(2), activation, which is a downstream target for MAPK and p38 MAPK. Profiling caspase enzymes activated by TNF in HeLa cells showed sequential caspase-8, -3, -7, -6 and -9 activation, with their inhibition characteristics suggesting a role for caspase-3 and/or caspase-6 in modulating JNK activity. Taken together these results show delineated ERK-activation pathways employed by TNFR subtypes.

    Original languageEnglish
    Pages (from-to)145-155
    Number of pages10
    JournalBiochemical Journal
    Volume366
    Issue numberPt 1
    Publication statusPublished - 2002

    Keywords

    • apoptosis
    • cytokine receptor
    • human
    • protein kinase/phosphatase
    • signal transduction
    • KAPPA-B ACTIVATION
    • CYTOSOLIC PHOSPHOLIPASE A(2)
    • APOPTOTIC CELL-DEATH
    • FACTOR TNF RECEPTOR
    • FACTOR-ALPHA
    • INDEPENDENT PATHWAYS
    • ARACHIDONIC-ACID
    • CYTOTOXICITY
    • INHIBITORS
    • CRMA

    Cite this

    Tumour necrosis factor-induced activation of c-Jun N-terminal kinase is sensitive to caspase-dependent modulation while activation of mitogen-activated protein kinase (MAPK) or p38 MAPK is not. / Mohamed, Ahmed; Jupp, O. J.; Anderson, H. M.; Littlejohn, Alison; Vandenabeele, P.; MacEwan, David Joseph.

    In: Biochemical Journal, Vol. 366, No. Pt 1, 2002, p. 145-155.

    Research output: Contribution to journalArticle

    Mohamed, Ahmed ; Jupp, O. J. ; Anderson, H. M. ; Littlejohn, Alison ; Vandenabeele, P. ; MacEwan, David Joseph. / Tumour necrosis factor-induced activation of c-Jun N-terminal kinase is sensitive to caspase-dependent modulation while activation of mitogen-activated protein kinase (MAPK) or p38 MAPK is not. In: Biochemical Journal. 2002 ; Vol. 366, No. Pt 1. pp. 145-155.
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    abstract = "The activation of the extracellular signal-regulated kinases (ERKs) by tumour necrosis factor-alpha (TNF) receptors (TNFRs) is an integral part of the cytokinc's pleiotropic cellular responses. Here we report differences in the caspase sensitivity and TNFR subtype activation of members of the ERK family. Inhibition in HeLa cells of caspase function by pharmacological inhibitors or the expression of CrmA (cytokine response modifier A), a viral modifier protein, blocks TNF-induced apoptosis or caspase-dependent protein kinase Cdelta and poly(ADP-ribose) polymerase protein degradation. TNFR1- or TNFR2-stimulated c-Jun N-terminal kinase (JNK) activity was attenuated in cells in which caspase activity was inhibited either by pharmacological blockers or CrmA expression. Both TNFR1- and TNFR2-stimulated JNK activity was caspase-sensitive; however, only TNFR1 was capable of stimulating p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK activities. TNFR1-stimulated p42/44 MAPK and p38 MAPK activities were insensitive to pharmacological caspase inhibition or CrmA. These findings were supported when measuring TNF-induced cytosolic phospholipase A(2), activation, which is a downstream target for MAPK and p38 MAPK. Profiling caspase enzymes activated by TNF in HeLa cells showed sequential caspase-8, -3, -7, -6 and -9 activation, with their inhibition characteristics suggesting a role for caspase-3 and/or caspase-6 in modulating JNK activity. Taken together these results show delineated ERK-activation pathways employed by TNFR subtypes.",
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    TY - JOUR

    T1 - Tumour necrosis factor-induced activation of c-Jun N-terminal kinase is sensitive to caspase-dependent modulation while activation of mitogen-activated protein kinase (MAPK) or p38 MAPK is not

    AU - Mohamed, Ahmed

    AU - Jupp, O. J.

    AU - Anderson, H. M.

    AU - Littlejohn, Alison

    AU - Vandenabeele, P.

    AU - MacEwan, David Joseph

    PY - 2002

    Y1 - 2002

    N2 - The activation of the extracellular signal-regulated kinases (ERKs) by tumour necrosis factor-alpha (TNF) receptors (TNFRs) is an integral part of the cytokinc's pleiotropic cellular responses. Here we report differences in the caspase sensitivity and TNFR subtype activation of members of the ERK family. Inhibition in HeLa cells of caspase function by pharmacological inhibitors or the expression of CrmA (cytokine response modifier A), a viral modifier protein, blocks TNF-induced apoptosis or caspase-dependent protein kinase Cdelta and poly(ADP-ribose) polymerase protein degradation. TNFR1- or TNFR2-stimulated c-Jun N-terminal kinase (JNK) activity was attenuated in cells in which caspase activity was inhibited either by pharmacological blockers or CrmA expression. Both TNFR1- and TNFR2-stimulated JNK activity was caspase-sensitive; however, only TNFR1 was capable of stimulating p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK activities. TNFR1-stimulated p42/44 MAPK and p38 MAPK activities were insensitive to pharmacological caspase inhibition or CrmA. These findings were supported when measuring TNF-induced cytosolic phospholipase A(2), activation, which is a downstream target for MAPK and p38 MAPK. Profiling caspase enzymes activated by TNF in HeLa cells showed sequential caspase-8, -3, -7, -6 and -9 activation, with their inhibition characteristics suggesting a role for caspase-3 and/or caspase-6 in modulating JNK activity. Taken together these results show delineated ERK-activation pathways employed by TNFR subtypes.

    AB - The activation of the extracellular signal-regulated kinases (ERKs) by tumour necrosis factor-alpha (TNF) receptors (TNFRs) is an integral part of the cytokinc's pleiotropic cellular responses. Here we report differences in the caspase sensitivity and TNFR subtype activation of members of the ERK family. Inhibition in HeLa cells of caspase function by pharmacological inhibitors or the expression of CrmA (cytokine response modifier A), a viral modifier protein, blocks TNF-induced apoptosis or caspase-dependent protein kinase Cdelta and poly(ADP-ribose) polymerase protein degradation. TNFR1- or TNFR2-stimulated c-Jun N-terminal kinase (JNK) activity was attenuated in cells in which caspase activity was inhibited either by pharmacological blockers or CrmA expression. Both TNFR1- and TNFR2-stimulated JNK activity was caspase-sensitive; however, only TNFR1 was capable of stimulating p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK activities. TNFR1-stimulated p42/44 MAPK and p38 MAPK activities were insensitive to pharmacological caspase inhibition or CrmA. These findings were supported when measuring TNF-induced cytosolic phospholipase A(2), activation, which is a downstream target for MAPK and p38 MAPK. Profiling caspase enzymes activated by TNF in HeLa cells showed sequential caspase-8, -3, -7, -6 and -9 activation, with their inhibition characteristics suggesting a role for caspase-3 and/or caspase-6 in modulating JNK activity. Taken together these results show delineated ERK-activation pathways employed by TNFR subtypes.

    KW - apoptosis

    KW - cytokine receptor

    KW - human

    KW - protein kinase/phosphatase

    KW - signal transduction

    KW - KAPPA-B ACTIVATION

    KW - CYTOSOLIC PHOSPHOLIPASE A(2)

    KW - APOPTOTIC CELL-DEATH

    KW - FACTOR TNF RECEPTOR

    KW - FACTOR-ALPHA

    KW - INDEPENDENT PATHWAYS

    KW - ARACHIDONIC-ACID

    KW - CYTOTOXICITY

    KW - INHIBITORS

    KW - CRMA

    M3 - Article

    VL - 366

    SP - 145

    EP - 155

    JO - Biochemical Journal

    JF - Biochemical Journal

    SN - 0264-6021

    IS - Pt 1

    ER -