SIGNAL SEQUENCE PROCESSING IN ROUGH MICROSOMES

Secretory proteins are synthesized with a signal sequence that is usua lly cleaved from the nascent protein during the translocation of the p olypeptide chain into the lumen of the endoplasmic reticulum. To deter mine the fate of a cleaved signal sequence, we used a synchronized in vitro translocation system. Fire found that the cleaved signal peptide of preprolactin is further processed close to its COOH terminus. The resulting fragment accumulated in the microsomal fraction and with tim e was released into the cytosol. Signal sequence cleavage and processi ng could be reproduced with reconstituted vesicles containing Sec61, s ignal recognition particle receptor, and signal peptidase complex.