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 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 suggest that besides L58, S54 particularly, but also E52, S53, K55 and E56 contribute to gp130 activation.
Brakenhoff
J P
JP
Department of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
Bos
H K
HK
Grötzinger
J
J
Rose-John
S
S
Aarden
L A
LA
D000409:Alanine; D015703:Antigens, CD / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D050822:Cytokine Receptor gp130; D004926:Escherichia coli; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology*; D008958:Models, Molecular; D009101:Multiple Myeloma; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130; D000409:Alanine