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Somatic mutagenesis studies of NF-κB signaling in human T cells: evidence for an essential role of IKKγ in NF-κB activation by T-cell costimulatory signals and HTLV-I Tax protein.
- Source :
- Oncogene; 3/9/2000, Vol. 19 Issue 11, p1448, 9p
- Publication Year :
- 2000
-
Abstract
- NF-κB plays a pivotal role in normal T-cell activation and may also mediate human T-cell leukemia virus (HTLV)-induced T-cell transformation. Activation of NF-κB by both T-cell costimulatory signals and the HTLV Tax protein involves stimulation of IκB kinase (IKK). As a genetic approach to dissect the intermediate steps involved in NF-κB activation in human T cells, we performed somatic cell mutagenesis to isolate signaling-defective mutant Jurkat T-cell lines. One of the mutant cell lines was shown to have a specific blockade in the IKK signaling pathway but remained competent in the c-Jun N-terminal kinase and MAP kinase pathways. Interestingly, this mutant cell line lacks expression of IKKγ, a non-catalytic component of the IKK complex. Expression of exogenous IKKγ in the mutant cells restored NF-κB activation by both the T-cell costimulation agents and Tax. These findings provide genetic evidence for the requirement of IKKγ in NF-κB signaling triggered by both T-cell costimulatory signals and HTLV-I Tax protein. Oncogene (2000) 19, 1448–1456. [ABSTRACT FROM AUTHOR]
- Subjects :
- MUTAGENESIS
SOMATIC cells
NF-kappa B
T cells
HTLV-I
Subjects
Details
- Language :
- English
- ISSN :
- 09509232
- Volume :
- 19
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 8911516
- Full Text :
- https://doi.org/10.1038/sj.onc.1203445