Aspartic acid residue 124 in the third transmembrane domain of the somatostatin receptor subtype 3 is essential for somatostatin-14 binding

DNA Cell Biol. 1995 Nov;14(11):939-44. doi: 10.1089/dna.1995.14.939.


A highly conserved aspartic acid residue present in the third membrane-spanning region of adrenergic and muscarinic receptors is directly involved in ligand binding. The five cloned somatostatin receptor subtypes also contain this residue at the same relative position. To test whether Asp-124 of the rat somatostatin receptor subtype 3 (SSTR3) is responsible for the binding of somatostain-14 (SST-14), this amino acid residue was replaced by an asparagine or a glutamic acid by polymerase chain reaction (PCR)-mediated site-directed mutagenesis. Expression and binding activity of the wild-type and mutant receptor constructs were studied in COS and HEK cells by ligand binding, UV cross-linking, Western blot, and immunocytochemical analysis. The Asn or Glu mutations result in a significant loss of SST-14 binding, although the mutant receptors are correctly transferred to the cell surface, demonstrating that Asp-124 is directly involved in binding of SST-14.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aspartic Acid / metabolism*
  • Base Sequence
  • Cell Line
  • Cell Membrane / chemistry
  • Chlorocebus aethiops
  • Humans
  • Kidney / embryology
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Rats
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Somatostatin / metabolism*
  • Transfection


  • Receptors, Somatostatin
  • Recombinant Fusion Proteins
  • Aspartic Acid
  • Somatostatin