TY - JOUR
T1 - Requirement of posttranslational modifications for the generation of biologic activity of glycosylation-inhibiting factor
AU - Liu, Yun Cai
AU - Nakano, Tatsumi
AU - Elly, Christian
AU - Ishizaka, Kimishige
PY - 1994/11/8
Y1 - 1994/11/8
N2 - Secretion of bioactive glycosylation-inhibiting factor (GIF) appears to be restricted to suppressor T (T(s)) cells, although various human and murine cell line cells secrete the 13-kDa peptide that reacts with anti-GIF. Nucleotide sequences of GIF cDNA from the T(s) and non-T(s) cells are identical, indicating that bioactive GIF and inactive GIF have an identical amino acid sequence. A stable transfectant of human GIF (hGIF) cDNA in BMT10 cells secretes inactive GIF peptide, whereas transfection of a chimeric cDNA encoding a fusion protein consisting of the N-terminal region of procalcitonin precursor and hGIF into the same cells results in secretion of bioactive GIF. Evidence was obtained that the fusion protein goes into the endoplasmic reticulum and is cleaved for the secretion of mature GIF peptide, whereas the inactive 13-kDa peptide synthesized by the former transfectant does not go through the endoplasmic reticulum. However, a stable transfectant of hGIF cDNA in mouse T(s) hybridoma contains inactive GIF in the cytosol and secretes bioactive hGIF without participation of the endoplasmic reticulum- Golgi system. Heterogeneity of the 13-kDa hGIF from the transfectant was detected in two-dimensional electrophoresis. The results suggested that T(s) cells have a machinery that converts a portion of inactive cytosolic GIF peptide to bioactive GIF during secretion.
AB - Secretion of bioactive glycosylation-inhibiting factor (GIF) appears to be restricted to suppressor T (T(s)) cells, although various human and murine cell line cells secrete the 13-kDa peptide that reacts with anti-GIF. Nucleotide sequences of GIF cDNA from the T(s) and non-T(s) cells are identical, indicating that bioactive GIF and inactive GIF have an identical amino acid sequence. A stable transfectant of human GIF (hGIF) cDNA in BMT10 cells secretes inactive GIF peptide, whereas transfection of a chimeric cDNA encoding a fusion protein consisting of the N-terminal region of procalcitonin precursor and hGIF into the same cells results in secretion of bioactive GIF. Evidence was obtained that the fusion protein goes into the endoplasmic reticulum and is cleaved for the secretion of mature GIF peptide, whereas the inactive 13-kDa peptide synthesized by the former transfectant does not go through the endoplasmic reticulum. However, a stable transfectant of hGIF cDNA in mouse T(s) hybridoma contains inactive GIF in the cytosol and secretes bioactive hGIF without participation of the endoplasmic reticulum- Golgi system. Heterogeneity of the 13-kDa hGIF from the transfectant was detected in two-dimensional electrophoresis. The results suggested that T(s) cells have a machinery that converts a portion of inactive cytosolic GIF peptide to bioactive GIF during secretion.
KW - endoplasmic reticulum
KW - macrophage-migration inhibitory factor
KW - suppressor T cells
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U2 - 10.1073/pnas.91.23.11227
DO - 10.1073/pnas.91.23.11227
M3 - Article
C2 - 7972039
AN - SCOPUS:0027994720
SN - 0027-8424
VL - 91
SP - 11227
EP - 11231
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -