T lymphocytes constitutively produce an interferonlike cytokine limitin characterized as a heat- and acid-stable and heparin-binding glycoprotein.
Several reports have described "multifunctional" eukaryotic mRNAs producing more than one protein through alternative translational initiation at multiple AUG codons. There are 2 such codons in the 5' region of our recently cloned limitin gene where 2 open reading frames overlap by 34 nucleotides. The deduced protein translated from the first ATG contains 33 amino acids, lacks a signal peptide, and has no obvious effects on the transfected 293T cells. We found that the second ATG is more effective as a translational initiation site than the first ATG and yields a secreted protein of 182 amino acids with the same activity as products made with full-length limitin cDNA. Immunohistochemical and reverse transcription-polymerase chain reaction analysis revealed that the longer limitin protein is produced by mature T lymphocytes in spleen and thymus as well as by bronchial epithelial and salivary duct cells in healthy mice. Properties of recombinant limitin were determined, revealing it to be a serologically distinct, heat- and acid-stable, heparin-binding glycoprotein with the potential for dimerization. Although the longer limitin protein is structurally and characteristically related to type I interferons, its production is uniquely regulated by translation as well as transcription.
Oritani
Kenji
K
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan. oritani@imed2.med.osaka-u.ac.jp
Hirota
Seiichi
S
Nakagawa
Taishirou
T
Takahashi
Isao
I
Kawamoto
Shin-Ichiro
S
Yamada
Masahide
M
Ishida
Naoko
N
Kadoya
Toshihiko
T
Tomiyama
Yoshiaki
Y
Kincade
Paul W
PW
Matsuzawa
Yuji
Y
D000143:Acids / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D018387:Codon, Initiator; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D006031:Glycosylation; D006493:Heparin / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D007372:Interferons; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011485:Protein Binding; D013601:T-Lymphocytes / Q000378:metabolism*; D014018:Tissue Distribution
D000143:Acids; D018387:Codon, Initiator; D016207:Cytokines; C410906:limitin; D006493:Heparin; D007372:Interferons