Cleavage of nascent UDP glucuronosyltransferase from rat liver by dog pancreatic microsomes.

Antibody to mouse UDP glucuronosyltransferase, previously shown to cross-react with rat transferase [1], immunoadsorbed 3 electrophoretically distinct transferase forms from the microsomes of untreated and phenobarbital-treated rats and 4 forms from 3-methylcholanthrene treated animals. The forms from phenobarbital-treated or control animals ranged in molecular weights from 49,000 to 52,000 daltons, and those from 3-methylcholanthrene-treated rats ranged from 51,000 to 57,000 daltons. The intensity of the electrophoretic bands indicated that the levels of at least two forms were increased by the administration of either compound. In contrast, only a 52,000-dalton electrophoretic band was observed after immunoadsorption of in vitro translated products using poly(A) RNA isolated from either control, phenobarbital-, or 3-methylcholanthrene-treated rats. When dog pancreatic microsomes were included in the in vitro translation assay for either of the poly(A) RNA preparations, part of the 52,000-dalton band remained and a new band of about 50,000 daltons was generated. This processed transferase form(s) appeared to be inserted into or sequestered by the microsomes. These results indicate that some of the electrophoretic variants of rat liver transferase arise by posttranslational modifications and that at least one rat transferase form undergoes proteolytic cleavage of an approximate 2,000-dalton peptide fragment during insertion into the membrane.