A MAJOR PHOSPHOPROTEIN OF THE ENDOPLASMIC-RETICULUM IS PROTEIN DISULFIDE-ISOMERASE

One of the effects of ATP in the endoplasmic reticulum is to induce th e phosphorylation of several proteins among which a 57-kDa protein (pp 57) prevails in our labeling conditions. We provide evidence that pp57 is protein disulfide isomerase (PDI), an abundant ubiquitous protein of the endoplasmic reticulum involved in various important cellular fu nctions. This phosphorylation does not result from the activity of a m icrosomal protein kinase but from an autophosphorylation as described for other microsomal proteins such as chaperones. Phosphoamino acid an alysis and cyanogen bromide cleavage indicate that the modification si te lies on a threonine residue within the central region of the protei n outside the thioredoxin-like domains. For the pure PDI, only the dim er is able to phosphorylate, while some experiments suggest that withi n the endoplasmic reticulum the phosphorylated form of PDI is mainly m obilized in larger size oligomers. Thus a possible role for this phosp horylation may be to modulate the association of PDI with its differen t partners.