ADP-ribosylation of the 78-kDa glucose-regulated protein during nutritional stress

Starvation of a mouse hepatoma cell line, Hepa, for any essential amino acid results in the mono‐ADP‐ribosylation of an 80‐kDa protein, P80. The ADP‐ribose acceptor and its putative precursor were identified in two‐dimensional gel patterns and isolated by electroelution. Amino‐terminal sequence analysis showed they were the 78‐kDa glucose‐regulated protein, GRP78. Starvation of Hepa cells for tryptophan or glucose stimulated the relative rate of synthesis, and the ADP‐ribosylation of GRP78. Inhibition of N‐linked glycosylation by treatment with tunicamycin, 2‐deoxy‐d‐glucose or glucosamine stimulated the synthesis of non‐ADP‐ribosylated GRP78 up to sixfold with relatively little effect on its ADP‐ribosylation. Both forms were identified in mouse liver, lung, heart, kidney, spleen and brain.