TY - JOUR
T1 - Amino-terminal sequences of prosomatostatin direct intracellular targeting but not processing specificity
AU - Sevarino, Kevin A.
AU - Stork, Philip
AU - Ventimiglia, Roseann
AU - Mandel, Gail
AU - Goodman, Richard H.
N1 - Funding Information:
We gratefully acknowledge R. Felix, C. Banks, and A. Ronco for technical assistance. We thank C. Herteaux for assisting with the in situ hybridizations and A. Nguyen for assistance with the a(l)PPSS construction. We acknowledge the generous gifts of synthetic a(ll)SS-14 and a(ll)SS-26 provided by J. Rivier, Clayton Biology Laboratory, Salk Institute, La Jolla, CA, and antiserum R293D provided by B. Noe. We also thank D. Faller for the plasmid pxf-MoA, W. Rutter for the plasmid pLAS2, and J. Kopchick for the plasmid CMV-Bglll. This work was supported by grants from the National Institutes of Health (DK31400, lP30 AM34926). K. A. S. was the recipient of a postdoctoral fellowship from the Juvenile Diabetes Foundation.
PY - 1989/4/7
Y1 - 1989/4/7
N2 - 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.
AB - 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.
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U2 - 10.1016/0092-8674(89)90167-0
DO - 10.1016/0092-8674(89)90167-0
M3 - Article
C2 - 2564811
AN - SCOPUS:0024593402
SN - 0092-8674
VL - 57
SP - 11
EP - 19
JO - Cell
JF - Cell
IS - 1
ER -