Liu Y C, Nakano T, Elly C, Ishizaka K
Division of Immunobiology, La Jolla Institute for Allergy and Immunology, CA 92037.
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11227-31. doi: 10.1073/pnas.91.23.11227.
Secretion of bioactive glycosylation-inhibiting factor (GIF) appears to be restricted to suppressor T (Ts) 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 Ts and non-Ts 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 Ts 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 Ts cells have a machinery that converts a portion of inactive cytosolic GIF peptide to bioactive GIF during secretion.
生物活性糖基化抑制因子（GIF）的分泌似乎仅限于抑制性T（Ts）细胞，尽管各种人和小鼠细胞系细胞都会分泌与抗GIF反应的13 kDa肽。来自Ts细胞和非Ts细胞的GIF cDNA核苷酸序列相同，这表明生物活性GIF和无活性GIF具有相同的氨基酸序列。BMT10细胞中人类GIF（hGIF）cDNA的稳定转染子分泌无活性的GIF肽，而将编码由降钙素原前体N端区域和hGIF组成的融合蛋白的嵌合cDNA转染到同一细胞中，则会分泌生物活性GIF。有证据表明，融合蛋白进入内质网并被切割以分泌成熟的GIF肽，而前一转染子合成的无活性13 kDa肽不经过内质网。然而，小鼠Ts杂交瘤中hGIF cDNA的稳定转染子在细胞质中含有无活性GIF，并在内质网-高尔基体系统不参与的情况下分泌生物活性hGIF。在二维电泳中检测到转染子中13 kDa hGIF的异质性。结果表明，Ts细胞具有一种机制，可在分泌过程中将一部分无活性的细胞质GIF肽转化为生物活性GIF。
