Human interferon gamma potently induces the synthesis of a 55-kDa protein (gamma 2) highly homologous to rabbit peptide chain release factor and bovine tryptophanyl-tRNA synthetase.
An interferon gamma (IFN-gamma)-inducible protein, gamma 2, was identified by two-dimensional gel electrophoresis of transformed human amnion (AMA) cell proteins. cDNA clones coding for this protein have been isolated and characterized as encoding a polypeptide with a predicted molecular weight of 53,165 and a pI of 6.16. Both values are in good agreement with those observed in two-dimensional gel electrophoresis. The gamma 2 protein is found to be highly induced by IFN-gamma, whereas no induction was seen after addition of IFN-alpha to AMA cells. A gamma 2-specific 2.7-kilobase mRNA was likewise seen to accumulate selectively in response to IFN-gamma in these cells. Comparison of the predicted amino acid sequence of gamma 2 to proteins in GenBank data bases revealed that gamma 2 is highly homologous to rabbit peptide chain release factor [Lee, C. C., Craigen, W. J., Muzny, D. M., Harlow, E. & Caskey, C. T. (1990) Proc. Natl. Acad. Sci. USA 87, 3508-3512] and bovine tryptophanyl-tRNA synthetase [M. Garret, V. Trezeguet, B. Pajot, J. C. Gandar, M. Merle, M. Guegiev, J. P. Benedetto, C. Sarger, J. Alteriot, J. La Bouessec, J. Labouesse, and J. Bonnet (1990), GenBank accession no. X52113]. Amino acid sequence similarities of 94% and 97%, respectively, are found, which in general would indicate that gamma 2 represents the human equivalent to either of these two mammalian genes. Based on these sequence similarities, the current data raise the possibility that tryptophanyl-tRNA charging and peptide chain release are carried out by the same enzyme. The gamma 2 protein is shown to possess tryptophan-dependent aminoacyl-tRNA synthetase activity and thus constitutes an enzymatic activity involved in the biological activity of IFN-gamma.
Fleckner
J
J
Department of Molecular Biology, University of Aarhus, Denmark.
Rasmussen
H H
HH
Justesen
J
J
D000595:Amino Acid Sequence; D000650:Amnion / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010454:Peptide Termination Factors / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011817:Rabbits; D011994:Recombinant Proteins; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014369:Tryptophan-tRNA Ligase / Q000235:genetics* / Q000378:metabolism
D009838:Oligodeoxyribonucleotides; D010454:Peptide Termination Factors; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C070289:peptide chain release factor, mammalian; D007371:Interferon-gamma; D014369:Tryptophan-tRNA Ligase