Construction and functional analysis of hybrid interleukin-6 variants. Characterization of the role of the C-terminus for species specificity.
We have constructed several hybrid human interleukin-6 (IL-6) variants in which the carboxyl-terminus, which includes a receptor binding site of IL-6 has been replaced with the C-terminus of various proteins homologous to human IL-6. IL-6 hybrids with the C-terminus of human growth hormone and human granulocyte-colony stimulating factor maintain part of the biological activity of human IL-6. Replacing the C-terminus of human IL-6 with the C-terminus of mouse and rat IL-6 resulted in a normal or increased activity on a mouse cell line; however, this gave a low (to 200-fold less) activity on a human cell line compared to wild-type human IL-6. We therefore conclude that the C-terminus of IL-6 plays an important role in the species specificity of IL-6.
Leebeek
F W
FW
University of North Carolina, Department of Pathology, Chapel Hill.
Fowlkes
D M
DM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D051381:Rats; D016415:Sequence Alignment; D013045:Species Specificity
D015850:Interleukin-6; D004247:DNA