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Biosynthesis of Rat Preprosomatostatin

  • Richard H. Goodman
  • Marc R. Montminy
  • Malcolm J. Low
  • Joel F. Habener
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 188)

Abstract

The biologically active forms of somatostatin, somatostatin-14 (SS-14) and somatostatin-28 (SS-28) arise by post-translational cleavage of prosomatostatin. Prosomatostatin in turn is derived from a larger precursor, preprosomatostatin. We have previously reported the structure of a complementary DNA moelcule encoding rat preprosomatostatin. The nucleotide sequence of this cDNA indicated that SS-14 and SS-28 are located at the carboxy-terminus of a 116 amino acid precursor. At the amino-terminus of the precursor is a hydrophobic region characteristic of a leader or pre-sequence. Sequential Edman degradations of cell-free translation products synthesized in the presence of microsomal membranes indicate that preprosomatostatin is cleaved within the endoplasmic reticulum to form prosomatostatin, a precursor of 92 amino acids. To begin to elucidate the factors which regulate the expression of the rat somatostatin gene, we have determined the sequence of the gene isolated from recombinant bacteriophage libraries. The gene spans 1.2 kilobases in length and is interrupted within the coding sequence of prosomatostatin by a single intron of 630 bases. A variant of the Goldberg-Hogness promoter, TTTAAA, is located 31 bases upstream from the transcriptional start point. A repetitive sequence was identified in the 5' region of the gene within 650 bases of the promoter. The nucleotide sequence of this region reveals an alternating GT sequence 42 bases in length characteristic of DNA with Z-forming potential. Such sequences are thought to influence the expression of other eukaryotic genes.

Keywords

Microsomal Membrane High Molecular Weight Form Sequential Edman Degradation Hydrophobic Leader Sequence Porcine Hypothalamus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Richard H. Goodman
    • 1
  • Marc R. Montminy
    • 1
  • Malcolm J. Low
    • 1
  • Joel F. Habener
    • 2
  1. 1.Division of EndocrinologyTufts New England Medical CenterBostonUSA
  2. 2.Laboratory of Molecular Endocrinology, Howard Hughes Medical InstituteMassachusetts General HospitalBostonUSA

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