Tissue-specific posttranslational processing of pre-prosomatostatin encoded by a metallothionein-somatostatin fusion gene in transgenic mice.
The somatostatins are neuropeptides of 14 and 28 amino acids that inhibit the release of growth hormone and other hypophyseal and gastrointestinal peptides. These neuropeptides are cleaved posttranslationally from a common precursor, pre-prosomatostatin. We report here the production and processing of pre-prosomatostatin by transgenic mice carrying a metallothionein-somatostatin fusion gene. The most active site of somatostatin production, as determined by hormone concentrations in the tissues, is the anterior pituitary, a tissue that does not normally synthesize somatostatin-like peptides. Anterior pituitary processed pre-prosomatostatin almost exclusively to the two biologically active peptides, somatostatin-14 and somatostatin-28, whereas the liver and kidney synthesized much smaller quantities of predominantly a 6000 dalton somatostatin-like peptide. The growth of the transgenic mice was normal despite high plasma levels of the somatostatin-like peptides. These studies indicate that proteases which cleave prosomatostatin to somatostatin-28 and somatostatin-14 are not specific to tissues that normally express somatostatin.
Low
M J
MJ
Hammer
R E
RE
Goodman
R H
RH
Habener
J F
JF
Palmiter
R D
RD
Brinster
R L
RL
D000818:Animals; D004274:DNA, Recombinant; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D009928:Organ Specificity; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013004:Somatostatin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
D004274:DNA, Recombinant; D011498:Protein Precursors; D013004:Somatostatin; D008668:Metallothionein