Modulation of the Phosphorylation of Glucose-Regulated Protein, GRP78, by Transformation and Inhibition of Glycosylation

The phosphorylation of glucose-regulated protein, GRP78, is thought to be involved in the regulation of the binding function of GRP78 to immunoglobulin heavy chains. The phosphorylation of GRP78 proceeded faster in transformed cells than in normal cells, whereas the levels of GRP78 synthesis and accumulation were similar in both cells. Treatment of the cells with tunicamycin caused a rapid decrease in GRP78 phosphorylation within 2 to 4 h in both cell types prior to GRP78 induction. Following a longer period of tunicamycin treatment, GRP78 phosphorylation recovered gradually in parallel with the accumulation of newly synthesized GRP78. The half-life of GRP78 was over 24 h and similar in both normal and transformed cells either with or without tunicamycin treatment. In contrast, the half-life of phosphate groups incorporated into GRP78 was about 120 min in both types of cells in the absence of tunicamycin treatment. When the cells were treated with tunicamycin, the half-life of the phosphate groups was shortened (-30 min) only in transformed cells, while it remained at untreated control levels in normal cells. These results suggest that GRP78 phosphorylation is important in functional regulation, and that the cells may carry out particular requirements such as increasing or decreasing secretory proteins by modulating GRP78 phosphorylation rather than GRP78 synthesis.