Amino-terminal sequences of prosomatostatin direct intracellular targeting but not processing specificity.
Rat preprosomatostatin (rPPSS) is processed to two bioactive peptides, somatostatin-14 and somatostatin-28. In anglerfish islets, the two peptides are synthesized by distinct cell types and are derived from different precursors, anglerfish preprosomatostatin-1 (a(I)PPSS) and anglerfish preprosomatostatin-2 (a(II)PPSS). To determine the basis of the differential processing, we introduced a(I)PPSS or a(II)PPSS expression vectors into mammalian endocrine cell lines that can accomplish both patterns of processing. Both precursors were processed identically, indicating that cellular factors must determine the processing pattern. Although similar processing sites are present in both precursors, high levels of unprocessed anglerfish prosomatostatin-2 were secreted constitutively from the transfected cells. A hybrid protein containing the leader sequence and a portion of the pro-region of rPPSS fused to the carboxy-terminal third of a(II)PPSS was processed and secreted via a regulated pathway. We conclude that the amino-terminal 78 residues of rPPSS contain sufficient information to correct the targeting deficiency of a(II)PPSS in mammalian endocrine cell lines.
Sevarino
K A
KA
Department of Medicine, New England Medical Center Hospital, Boston, Massachusetts 02111.
Stork
P
P
Ventimiglia
R
R
Mandel
G
G
Goodman
R H
RH
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005399:Fishes; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000032:analysis / Q000166:cytology / Q000378:metabolism; D051379:Mice; D011498:Protein Precursors / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D013004:Somatostatin / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D014162:Transfection
D011498:Protein Precursors; D013004:Somatostatin; C028456:prosomatostatin