Precursor structure, expression, and tissue distribution of human guanylin

Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9089-93. doi: 10.1073/pnas.89.19.9089.

Abstract

Heat-stable enterotoxins (STa) are small, cysteine-rich peptides secreted by Escherichia coli that are able to induce diarrhea through the stimulation of an intestine-specific receptor-guanylyl cyclase known as STaR. A 15-amino acid peptide, guanylin, was recently purified from rat jejunum and proposed to be a potential endogenous activator of this receptor. We describe here the cloning and characterization of human and mouse cDNAs encoding precursor proteins of 115 and 116 amino acids, respectively, having guanylin present at their C termini. Expression of the human cDNA in mammalian cells leads to the secretion of proguanylin, an inactive 94-amino acid protein. Guanylin generated by either trypsin or acid treatment of proguanylin was purified and found to bind to, and activate, STaR. Northern blot and in situ hybridization show high-level expression of guanylin mRNA restricted to the intestine, with localization to Paneth cells at the base of the small intestinal crypts. These results demonstrate that guanylin is an endogenous activator of STaR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Cloning, Molecular
  • DNA / genetics
  • DNA / isolation & purification
  • Gastrointestinal Hormones*
  • Gene Expression
  • Humans
  • In Situ Hybridization
  • Intestine, Small / physiology
  • Mice
  • Molecular Sequence Data
  • Natriuretic Peptides
  • Oligonucleotide Probes
  • Organ Specificity
  • Peptides / genetics*
  • Peptides / metabolism
  • Protein Precursors / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Gastrointestinal Hormones
  • Natriuretic Peptides
  • Oligonucleotide Probes
  • Peptides
  • Protein Precursors
  • RNA, Messenger
  • guanylin
  • DNA

Associated data

  • GENBANK/M95174
  • GENBANK/M95175