OVEREXPRESSION OF GRP78 MITIGATES STRESS INDUCTION OF GLUCOSE REGULATED PROTEINS AND BLOCKS SECRETION OF SELECTIVE PROTEINS IN CHINESE-HAMSTER OVARY CELLS
OVEREXPRESSION OF GRP78 MITIGATES STRESS INDUCTION OF GLUCOSE REGULATED PROTEINS AND BLOCKS SECRETION OF SELECTIVE PROTEINS IN CHINESE-HAMSTER OVARY CELLS
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DOI：
10.1002/j.1460-2075.1992.tb05201.x
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发表时间：
1992-04-01
期刊：
影响因子：
11.4
通讯作者：
KAUFMAN, RJ
中科院分区：
文献类型：
--
作者：
DORNER, AJ;WASLEY, LC;KAUFMAN, RJ
GRP 78是内质网（ER）的驻留蛋白，并且是葡萄糖调节蛋白（GRP）家族的成员。发现许多分泌缺陷蛋白与GRP 78稳定结合并保留在ER中。一些注定要分泌的蛋白质与GRP 78短暂结合。为了进一步加深我们对GRP 78在分泌中的作用的了解，我们在中国仓鼠卵巢（CHO）细胞中稳定过表达GRP 78，并检查了对蛋白质分泌和应激反应的影响。与野生型CHO细胞相比，用衣霉素或A23187处理的GRP 78过表达细胞表现出内源性GRP 78和GRP 94 mRNA的诱导减少。这表明GRP 78过表达加剧了应激或直接参与了应激诱导的GRPs表达的信号传导。分泌蛋白的瞬时表达用于测量GRP 78过表达细胞中的分泌效率。分泌的血管性血友病因子和突变形式的因子VIII，这两种蛋白质，瞬时与GRP 78，减少GRP 78过表达。与此相反，M-CSF的分泌（未检测到与GRP 78相关）不受影响。这表明升高的GRP 78水平可以增加稳定的缔合并降低通常与GRP 78瞬时缔合的蛋白质的分泌效率。这些结果表明，GRP 78的一个功能是选择性蛋白质保留在ER中。
GRP78 is a resident protein of the endoplasmic reticulum (ER) and a member of the glucose regulated protein (GRP) family. Many secretion incompetent proteins are found in stable association with GRP78 and are retained in the ER. Some proteins which are destined for secretion transiently associate with GRP78. To further increase our understanding of the role of GRP78 in secretion, we have stably overexpressed GRP78 in Chinese hamster ovary (CHO) cells and examined the effect on protein secretion and the stress response. GRP78 overexpressing cells treated with tunicamycin or A23187 exhibited a reduced induction of endogenous GRP78 and GRP94 mRNAs compared to wild-type CHO cells. This suggests that GRP78 overexpression either alleviates the stress or is directly involved in signaling stress-induced expression of GRPs. Transient expression of secreted proteins was used to measure secretion efficiency in the GRP78 overexpressing cells. Secretion of von Willebrand factor and a mutant form of factor VIII, two proteins which transiently associate with GRP78, was reduced by GRP78 overexpression. In contrast, secretion of M-CSF, which was not detected in association with GRP78, was unaffected. This indicates that elevated levels of GRP78 may increase stable association and decrease the secretion efficiency of proteins which normally transiently associate with GRP78. These results indicate that one function of GRP78 is selective protein retention in the ER.