| Autor: |
Brakenhoff JP; Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam., de Hon FD, Aarden LA |
| Jazyk: |
angličtina |
| Zdroj: |
Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 1995 Jul 21; Vol. 762, pp. 129-34; discussion 135. |
| DOI: |
10.1111/j.1749-6632.1995.tb32321.x |
| Abstrakt: |
We have shown that through mutagenesis of IL-6 it is possible to separate receptor binding from signal transduction of the cytokine. Mutations in residues important for signal transduction via gp130 result in IL-6 variants that can competitively inhibit wtIL-6 activity in vitro. The differential effects of these signaling deficient mutants on various cell lines of human origin suggest that receptor composition and/or signal transduction pathways may vary between cells of different origin. The observations that three sites have been identified which are important for gp130 interaction raises the question what the role of each region is in the stepwise formation of the active IL-6 receptor complex. The overall tertiary conformation of the beta-site mutants is intact, as judged from their binding characteristics to conformation specific mAbs and IL-6R alpha. As can be deduced from Figure 1, beta-site mutations may therefore affect a direct interaction with gp130, dimerization of IL-6, or maybe a conformational change in IL-6R alpha, important for gp130 interaction. A future challenge will therefore be to determine the function of each of the beta-sites in IL-6 receptor interaction. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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