Site-specific mutagenesis of human interleukin-6 and its biological activity.
Amino acid substitutions of human interleukin-6 (IL-6) were performed. Single substitution Met162----Ala and double substitutions Leu159.166----Val resulted in a significant decrease of IL-6 activity in the production of immunoglobulin (Ig) from B-cells. Single substitution Leu166----Val or Leu159----Val gave a slight or no significant decrease in the Ig-induction activity, respectively. The receptor-binding activity of each IL-6 mutant was also examined. It was observed that the decrease of the receptor-binding activity was generally in parallel with that of the Ig-induction activity. We therefore suggest that hydrophobic side-chains existing in Met162, Leu159, and Leu166 are significantly involved in the receptor-binding of IL-6.
Nishimura
C
C
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Futatsugi
K
K
Yasukawa
K
K
Kishimoto
T
T
Arata
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015345:Oligonucleotide Probes; D010957:Plasmids; D011971:Receptors, Immunologic / Q000378:metabolism; D019947:Receptors, Interleukin-6; D015183:Restriction Mapping; D014162:Transfection
D015850:Interleukin-6; D015345:Oligonucleotide Probes; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6