Herbimycin A blocks IL-1-induced NF-kappa B DNA-binding activity in lymphoid cell lines.
The mechanism by which interleukin-1 alpha (IL-1 alpha) activates NF-kappa B DNA-binding activity is not completely understood. While it is well established that protein kinase C can activate NF-kappa B, neither protein kinase C nor protein kinase A appears to be critical in the induction of NF-kappa B by IL-1 alpha. Since a number of growth factors signal via protein tyrosine kinase, in this study we examined a possible involvement of protein tyrosine kinase in the IL-1 alpha-induced NF-kappa B. The results showed that in the murine pre-B cell line 70Z/3 and in the murine T cell line EL-4 6.1 C10 IL-1 alpha-induced NF-kappa B was associated with transient increase in protein tyrosine kinase activity. Pre-treatment of these cell lines with herbimycin A, an inhibitor of tyrosine kinase activity, blocked the IL-1 alpha-enhanced protein tyrosine kinase activity and the IL-1 alpha-induced NF-kappa B DNA-binding activity. Herbimycin A at concentrations sufficient to block IL-1 alpha-induced NF-kappa B did not block the phorbol 12-myristate 13-acetate (PMA)-induced NF-kappa B. The data suggest that IL-1 alpha and PMA activate NF-kappa B by different pathways and that induction of NF-kappa B DNA-binding activity by IL-1 might be dependent on protein tyrosine phosphorylation.
Iwasaki
T
T
Department of Medicine, University of Washington, Seattle 98195.
Uehara
Y
Y
Graves
L
L
Rachie
N
N
Bomsztyk
K
K
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D016227:Benzoquinones; D004247:DNA / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007700:Kinetics; D047029:Lactams, Macrocyclic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D007375:Interleukin-1; D047029:Lactams, Macrocyclic; D016328:NF-kappa B; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D004247:DNA; D011505:Protein-Tyrosine Kinases