Dorner A J, Krane M G, Kaufman R J
Genetics Institute, Cambridge, Massachusetts 02140.
Mol Cell Biol. 1988 Oct;8(10):4063-70. doi: 10.1128/mcb.8.10.4063-4070.1988.
GRP78 is localized in the endoplasmic reticulum and associates with improperly folded or underglycosylated proteins. The role of GRP78 in secretion was studied in Chinese hamster ovary cells expressing a tissue plasminogen activator (tPA) variant which lacks potential N-linked glycosylation site sequences because of mutagenesis. The expression of variant tPA resulted in elevated levels of GRP78 and its stable association with tPA. The introduction of antisense GRP78 genes resulted in a two- to threefold reduction in GRP78 levels compared with those of the original cells. Cells with reduced levels of GRP78 secreted two- to threefold-higher levels of tPA activity. tPA expressed in these cells displayed reduced association with GRP78, and a greater proportion was processed to the mature form and secreted. These results demonstrate that reduction of GRP78 level can improve the secretion of an associated protein.
葡萄糖调节蛋白78（GRP78）定位于内质网，与折叠不当或糖基化不足的蛋白质相关联。在表达组织型纤溶酶原激活剂（tPA）变体的中国仓鼠卵巢细胞中研究了GRP78在分泌中的作用，该变体由于诱变而缺乏潜在的N-连接糖基化位点序列。变体tPA的表达导致GRP78水平升高及其与tPA的稳定结合。反义GRP78基因的引入导致GRP78水平比原始细胞降低两到三倍。GRP78水平降低的细胞分泌的tPA活性水平高出两到三倍。在这些细胞中表达的tPA与GRP78的结合减少，并且更大比例的tPA被加工成成熟形式并分泌。这些结果表明，GRP78水平的降低可以改善相关蛋白的分泌。
