Isolation and characterization of S. cerevisiae mutants defective in somatostatin expression: cloning and functional role of a yeast gene encoding an aspartyl protease in precursor processing at monobasic cleavage sites.

Publisher: Wiley Blackwell Country of Publication: England NLM ID: 8208664 Publication Model: Print Cited Medium: Print ISSN: 0261-4189 (Print) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE

Publication: 2014- : London : Wiley Blackwell
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-

Genes, Fungal* ; Proprotein Convertases* ; Protein Processing, Post-Translational* ; Saccharomyces cerevisiae Proteins* ; Subtilisins*; Aspartic Acid Endopeptidases/*genetics ; Aspartic Acid Endopeptidases/*metabolism ; Saccharomyces cerevisiae/*genetics ; Serine Endopeptidases/*metabolism ; Somatostatin/*genetics; Amino Acid Sequence ; Animals ; Cloning, Molecular ; Fishes ; Mating Factor ; Molecular Sequence Data ; Mutagenesis ; Mutagenesis, Site-Directed ; Peptide Biosynthesis ; Peptides/genetics ; Pheromones/genetics ; Plasmids ; Protein Precursors/genetics ; Protein Precursors/metabolism ; Recombinant Fusion Proteins/biosynthesis ; Restriction Mapping ; Saccharomyces cerevisiae/enzymology ; Serine Endopeptidases/genetics ; Somatostatin/biosynthesis ; Somatostatin/metabolism

The peptide somatostatin exists as two different molecular species. In addition to the most common form, somatostatin-14, there is also a fourteen amino acid N-terminally extended form of the tetradecapeptide, somatostatin-28. Both peptides are synthesized as larger precursors containing paired basic and monobasic amino acids at their processing sites, which upon cleavage generate either somatostatin-14 or -28, respectively. In some species of fish two distinct, but homologous, precursors (prosomatostatin-I and -II) give rise to somatostatin-14 and -28, respectively. Whereas anglerfish prosomatostatin-II was previously shown to release exclusively somatostatin-28, the yeast Saccharomyces cerevisiae proteolytically matures the homologous prosomatostatin-I precursor to somatostatin-28 and -14 as well as to a lysine-extended form of somatostatin-14. The Kex2 endoprotease appears to be essential for the formation of lysine somatostatin-14 and is involved either directly or indirectly in the release of mature somatostatin-14. The isolation of yeast mutants defective in somatostatin-28 expression (sex mutant) allowed the cloning of a non-essential gene, which encodes an aspartyl protease, whose disruption severely affects the cleavage of mature somatostatin-28 from both somatostatin precursors. We conclude that two distinct endoproteases, which demonstrate some cross specificity in vivo, are involved in the proteolytic maturation of prosomatostatin at mono- and dibasic processing sites in yeast.

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0 (Peptides)
0 (Pheromones)
0 (Protein Precursors)
0 (Recombinant Fusion Proteins)
0 (Saccharomyces cerevisiae Proteins)
51110-01-1 (Somatostatin)
61194-02-3 (Mating Factor)
74315-46-1 (prosomatostatin)
EC 3.4.21.- (Proprotein Convertases)
EC 3.4.21.- (Serine Endopeptidases)
EC 3.4.21.- (Subtilisins)
EC 3.4.21.61 (KEX2 protein, S cerevisiae)
EC 3.4.23.- (Aspartic Acid Endopeptidases)

Date Created: 19930101 Date Completed: 19930310 Latest Revision: 20220511

20240829

PMC413204

10.1002/j.1460-2075.1993.tb05655.x

8094050