Vogel J P, Misra L M, Rose M D
Department of Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544-1014.
J Cell Biol. 1990 Jun;110(6):1885-95. doi: 10.1083/jcb.110.6.1885.
BiP/GRP78 is an essential member of the HSP70 family that resides in the lumen of the endoplasmic reticulum. In yeast, BiP/GRP78 is encoded by the KAR2 gene. A temperature sensitive mutation was isolated in KAR2 and found to cause a rapid block in protein secretion. Secretory precursors of a number of proteins (invertase, carboxypeptidase Y, alpha-factor, and BiP) accumulated that were characteristic of a block in translocation into the lumen of the ER. Protease protection experiments confirmed that the precursors accumulated on the cytoplasmic side of the ER membrane. Moreover, depletion of wild-type KAR2 protein also resulted in a block in translocation of secretory proteins. These results implicate BiP/GRP78 function in the continued translocation of proteins into the lumen of the ER.
BiP/GRP78是热休克蛋白70(HSP70)家族的重要成员,位于内质网腔中。在酵母中,BiP/GRP78由KAR2基因编码。在KAR2中分离出一个温度敏感突变,发现它会导致蛋白质分泌迅速受阻。多种蛋白质(转化酶、羧肽酶Y、α因子和BiP)的分泌前体积累,这是转运至内质网腔受阻的特征。蛋白酶保护实验证实,这些前体在内质网膜的细胞质一侧积累。此外,野生型KAR2蛋白的缺失也导致分泌蛋白转运受阻。这些结果表明BiP/GRP78在蛋白质持续转运至内质网腔中发挥作用。