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J. Biol. Chem., Vol. 265, Issue 14, 8339-8343, May, 1990
Protein kinase C-independent activation of nuclear factor kappa B by tumor necrosis factor
A Meichle, S Schutze, G Hensel, D Brunsing and M Kronke
Klinische Arbeitsgruppe der Max-Planck-Gesellschaft, Gottingen, Federal Republic of Germany.
Tumor necrosis factor (TNF) is one of the few physiological inducers of the
pleiotropic transcription factor NF kappa B. NF kappa B may play a central
role in mediating TNF's gene regulatory action; however, the molecular
mechanisms of TNF-induced NF kappa B activation are poorly understood. In
this study, we demonstrate with two human leukemic cell lines, K562 and
Jurkat, that TNF induces rapid and transient activation and translocation
of protein kinase C (PK-C) from the cytosol to the membranes, which is
followed by the emergence of kappa B-binding activity. In order to
investigate whether TNF-mediated PK-C activation can be linked to induction
of NF kappa B, we tried to block TNF action by use of various protein
kinase C inhibitors as well as down- regulation of PK-C. Preincubation of
Jurkat cells with protein kinase inhibitor H7 or staurosporine blocked PK-C
activation by either TNF or phorbol 12-myristate 12-acetate (PMA). This
pretreatment regimen completely inhibited NF kappa B activation by PMA. In
contrast, TNF's ability to induce NF kappa B remained unaffected. In
addition, NF kappa B was TNF-inducible in Jurkat cells depleted for PK-C by
long-term exposure to high dose phorbol ester. The data indicate that PK-C
is not required for NF kappa B activation by TNF and imply a novel, PK-C-
independent mechanism of physiological NF kappa B activation.

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Copyright © 1990 by the American Society for Biochemistry and Molecular Biology.
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