IDENTIFICATION OF RESIDUES IN THE PUTATIVE 5TH HELICAL REGION OF HUMAN INTERLEUKIN-6, IMPORTANT FOR ACTIVATION OF THE IL-6 SIGNAL TRANSDUCER, GP130

We have previously shown that L58 in the putative 5th helical region o f human interleukin-6 (IL-6) is important for activation of the IL-6 s ignal transducer gp130 [de Hon et al. (1995) FEBS Lett, 369, 187-191]. To further explore the importance of individual residues in this regi on for gp130 activation we have now combined Ala substitutions of resi dues E52, S53, S54, K55, E56, L58 and E60 with other substitutions in IL-6, known to affect gp130 activation (Q160E and T163P). The combinat ion mutant protein with L58A completely lost the capacity to induce th e proliferation of XG-1 myeloma cells, and could effectively antagoniz e wild type IL-6 activity on these cells. Moreover, the data suggest t hat besides L58, S54 particularly, but also E52, S53, K55 and E56 cont ribute to gp130 activation.