0000000000711694
AUTHOR
Lucien A. Aarden
Identification of residues in the putative 5th helical region of human interleukin-6, important for activation of the IL-6 signal transducer, gp130
AbstractWe have previously shown that L58 in the putative 5th helical region of human interleukin-6 (IL-6) is important for activation of the IL-6 signal transducer gp130 [de Hon et al. (1995) FEBS Lett. 369, 187–191]. To further explore the importance of individual residues in this region for gp130 activation we have now combined Ala substitutions of residues E52, S53, S54, K55, E56, L58 and E60 with other substitutions in IL-6, known to affect gp130 activation (Q160E and T163P). The combination mutant protein with L58A completely lost the capacity to induce the proliferation of XG-1 myeloma cells, and could effectively antagonize wild type IL-6 activity on these cells. Moreover, the data …
Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is important for activation of the IL-6 signal transducer, gp130
A model of the tertiary structure of human IL-6, derived from the crystal-structure of granulocyte-colony stimulating factor, reveals a 5th helical region in the loop between the first and second alpha-helix. To investigate the importance of this region for biological activity of IL-6, residues Glu-52, Ser-53, Ser-54, Lys-55, Glu-56, Leu-58, and Glu-60 were individually replaced by alanine. IL-6.Leu-58Ala displayed a 5-fold reduced biological activity on the IL-6 responsive human cell lines XG-1 and A375. This reduction in bioactivity was shown to be due to a decreased capacity of the mutant protein to trigger IL-6 receptor-alpha-chain-dependent binding to the IL-6 signal transducer, gp130.