Tumor necrosis factors-alpha and -beta bind to the same two types of tumor necrosis factor receptors and maximally activate the transcription factor NF-kappa B at low receptor occupancy and within minutes after receptor binding.
HL60 cells have types A and B tumor necrosis factor (TNF) receptors whereas HEp2 cells have only the type B receptor (Hohmann, H.-P., Remy, R., Brockhaus, M., and van Loon, A.P.G.M. (1989) J. Biol. Chem. 264, 14927-14934). TNF-beta can be cross-linked to each of these receptors and competes with TNF-alpha for binding to both receptors. TNF-alpha and TNF-beta activate the transcription factor NF-kappa B in HL60 and HEp2 cells. Maximal activation of NF-kappa B required binding of TNF-alpha or TNF-beta to 20-25% of the total number of TNF receptors and was achieved within minutes after the addition of TNF-alpha to HL60 cells. Both TNF-alpha and TNF-beta activate NF-kappa B at 5-10-fold lower concentrations in HL60 cells compared with HEp2 cells, and this correlates well with their different affinities for binding to these cells. Thus, TNF-alpha and TNF-beta are indistinguishable with respect to the correlation between degrees of receptor binding and activation of NF-kappa B.
Hohmann
H P
HP
Central Research Units, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Remy
R
R
Pöschl
B
B
van Loon
A P
AP
D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D004268:DNA-Binding Proteins; D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha