Processing and intracellular sorting of anglerfish and rat preprosomatostatins in mammalian endocrine cells

Rat preprosomatostatin (rPPSS) is processed to two distinct end products in a tissue-specific manner. The analogous end products in anglerfish are derived from separate precursors, anglerfish preprosomatostatins-1 and -2 (a(1)PPSS and a(II)PPSS). This report reviews experiments demonstrating that in mammalian cells, the cell of expression, not precursor structure, determines the processing fate of the preprosomatostatins. A fusion precursor of a(II)PPSS and rPPSS was expressed in mammalian cell lines to determine that the amino-terminal 78 residues of rPPSS contain a sorting signal that directs the precursor into a regulated secretory pathway wherein proteolytic processing occurs. Preliminary studies of rPPSS pro-region mutations are presented that attempt to further localize this sorting signal.