Receptor-like properties of the 26 kDa transmembrane form of TNF.
Most members of the TNF family of proteins exist as transmembrane proteins with relatively long intracellular domains, and a number of them are involved in the ill-defined phenomenon of "reverse signaling". We have identified a putative nuclear localization signal in the cytoplasmic domain of TNF which proved to be functional in two assays. Western analysis identified an approximately 10 kDa peptide corresponding to the transmembrane and cytoplasmic domains of TNF after the proteolytic liberation of the 17 kDa, soluble form of TNF. This 10 kDa peptide was enriched in internal membranes and nuclear fractions of disrupted cells. Immune electron-microscopic studies proved its localization in transport vesicles and the nucleus. The nuclear transport of the intracellular segment of TNF resembles the signaling process through the Notch-type of receptors. Indeed, the presence of the 10 kDa peptide seems to influence the expression of another inflammatory cytokine, interleukin-1 beta. These findings suggest that the transmembrane form of TNF has receptor-like properties and its interaction with the receptors initiates a bidirectional signaling.
Domonkos
A
A
Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, H-6701 Szeged, P.O. Box 521, Hungary.
Udvardy
A
A
László
L
L
Nagy
T
T
Duda
E
E
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D007425:Intracellular Membranes / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D016207:Cytokines; D007375:Interleukin-1; D019913:Nuclear Localization Signals; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C061153:tumor necrosis factor precursor