Sequences of islet amyloid polypeptide precursors of an Old World monkey, the pig-tailed macaque (Macaca nemestrina), and the dog (Canis familiaris).
The 37-amino acid islet amyloid polypeptide represents the major protein component present in islet amyloid deposits. Although the presence of islet amyloid is a characteristic pathological feature of the islets of humans, monkeys and cats with Type 2 (non-insulin-dependent) diabetes mellitus, it is not found in the islets of diabetic rats, mice or dogs. To further explore the molecular basis for these species differences in amyloid deposition we have used a polymerase chain reaction based method to clone cDNAs encoding the monkey (Macaca nemestrina) and dog (Canis familiaris) islet amyloid polypeptide precursors. The predicted amino acid sequence of the monkey precursor is 96% identical to that of the human protein; differences include one replacement in the signal peptide and three in the islet amyloid polypeptide domain. The sequence of the dog precursor is most closely related to that of the cat protein (85% identity); the sequences of dog and cat islet amyloid polypeptide differ only at two positions and are identical in the region of amino acids 20-29, the region thought to be primarily responsible for amyloidogenesis. Thus, amino acid residues in addition to those at positions 20-29 may facilitate the aggregation of islet amyloid polypeptide. The presence of amyloid deposits in some dog pancreatic endocrine tumours suggests that the dog protein can be amyloidogenic, perhaps due to elevated expression of islet amyloid polypeptide by the tumours relative to normal islets.
Ohagi
S
S
Department of Biochemistry and Molecular Biology, University of Chicago.
Nishi
M
M
Bell
G I
GI
Ensinck
J W
JW
Steiner
D F
DF
D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004285:Dogs; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008214:Lymphocytes / Q000502:physiology; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010179:Pancreas / Q000502:physiology; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D009838:Oligodeoxyribonucleotides; D011498:Protein Precursors; D012313:RNA; D004247:DNA