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Gene Review

Gucy2c  -  guanylate cyclase 2c

Mus musculus

Synonyms: AI893437, GC-C, Gcc, Guanylyl cyclase C, Guc2c, ...
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Disease relevance of Gucy2c

  • In contrast, the absence of GC-C resulted in a reduction of median polyp number by 55% [1].
  • We show by in situ hybridization that GC-C expression is retained in adenomas from multiple intestinal neoplasia (Apc(Min/+)) mice [1].
  • GC-C is also the receptor for Escherichia coli heat-stable enterotoxin (STa) and activation by STa results in a diarrheal illness [2].
  • For uroguanylin two distinct signaling pathways exist in IHKE-1 cells, one involves GC-C and cGMP as second messenger, the other is cGMP-independent and connected to a pertussis toxin-sensitive G protein [3].
  • They activate enterocytes via guanylate cyclase C (GC-C), which leads to cGMP-dependent inhibition of Na+/H+ exchange and activation of the cystic fibrosis transmembrane regulator [4].

Psychiatry related information on Gucy2c


High impact information on Gucy2c


Chemical compound and disease context of Gucy2c


Biological context of Gucy2c

  • CONCLUSION: GN, UGN, and STa act on the mouse kidney, in part, through a cGMP-dependent, GC-C-independent mechanism, causing significant natriuresis by renal tubular processes [8].
  • Glomerular filtration rate (GFR), blood pressure, and plasma cGMP in the mice (wild-type or GC-C(-/-) null) did not significantly vary between the vehicle- and peptide-treatment groups [8].
  • Guanylyl cyclase C (GC-C), a transmembrane receptor for bacterial heat-stable enterotoxin and the mammalian peptides guanylin and uroguanylin, mediates intestinal ion secretion and affects intestinal cell growth via cyclic GMP signaling [1].
  • The presence of GC-C in mouse intestinal crypts supports the putative role of GC-C in fluid and electrolyte homeostasis and resembles the pattern in human tissues [9].
  • The human E. coli heat-stable enterotoxin (ST(h), amino acid sequence N1SSNYCCELCCNPACTGCY19) binds specifically to the guanylate cyclase C (GC-C) receptor, which is present in high density on the apical surface of normal intestinal epithelial cells as well as on the surface of human colon cancer cells [10].

Anatomical context of Gucy2c

  • GC-C mRNA was present in mouse intestine by embryonic day 12, and was expressed at high levels in both crypts and villus or surface epithelium of adult small intestine and colon, respectively [9].
  • Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C [11].
  • The evidence presented here suggests that in addition to ST(h) binding to GC-C expressing cell lines derived from human colon, ST(h) also specifically binds to an as yet unidentified receptor expressed in high densities on the surface of cell lines derived from human breast cancers [12].
  • These promoter elements were not active upon transfection into NIH/3T3 and LLC-PK1 cell lines which do not express GC-C [13].

Associations of Gucy2c with chemical compounds

  • Uroguanylin expression was significantly lower in GC-C-/- mice than in GC-A-/- and wild-types, suggesting that absence of a receptor was able to down-regulate ligand expression [14].
  • We postulated that the GC-C receptor plays an important role in acid-stimulated HCO3- secretion [15].
  • Indeed, GCC expressed in mammalian cells is tyrosine phosphorylated, suggesting that tyrosine phosphorylation may play a role in regulation of GCC signalling [7].

Physical interactions of Gucy2c

  • Thus, uroguanylin and guanylin seem to serve as intestinal and renal natriuretic peptide-hormones influencing salt and water transport in the kidney through GC-C dependent and independent pathways [2].

Regulatory relationships of Gucy2c

  • Guanylin and uroguanylin are peptides that activate guanylyl cyclase C (GC-C) receptors in the intestine and kidney, which causes an increase in the excretion of salt and water [5].

Other interactions of Gucy2c

  • Somatic loss of the wild-type Apc allele, an initiating event in intestinal tumorigenesis, also occurred in polyps from GC-C-deficient Apc(Min/+) mice [1].

Analytical, diagnostic and therapeutic context of Gucy2c

  • Expression was determined in 1) wild-type mice, 2) two strains of receptor-guanylyl cyclase-deficient mice (ANP-receptor-deficient, GC-A-/-, and GC-C-deficient mice); and 3) cultured renal epithelial (M-1) cells, by RT-PCR, Northern blotting and immunocytochemistry [14].
  • In vivo perfusion studies performed in wild-type (WT) and GC-C knockout (KO) mice indicated that acid-stimulated duodenal HCO3- secretion was significantly decreased in the GC-C KO animals compared with the WT counterparts [15].
  • We characterized the expression of GC-C in the mouse by Northern blot, in situ hybridization, and ligand binding studies [9].
  • Furthermore, (99m)Tc-NC100586 did not selectively accumulate in Lewis lung tumor xenografts, which do not express GC-C [16].
  • mRNA-based technologies and preclinical research in a variety of animal models have shown that guanylyl cyclase C (GCC) is a highly sensitive and specific molecular marker for the diagnosis of colorectal cancer (CRC) [17].


  1. Lack of guanylyl cyclase C, the receptor for Escherichia coli heat-stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model. Mann, E.A., Steinbrecher, K.A., Stroup, C., Witte, D.P., Cohen, M.B., Giannella, R.A. Int. J. Cancer (2005) [Pubmed]
  2. Renal effects of uroguanylin and guanylin in vivo. Carrithers, S.L., Hill, M.J., Johnson, B.R., O'Hara, S.M., Jackson, B.A., Ott, C.E., Lorenz, J., Mann, E.A., Giannella, R.A., Forte, L.R., Greenberg, R.N. Braz. J. Med. Biol. Res. (1999) [Pubmed]
  3. Guanylin, uroguanylin, and heat-stable euterotoxin activate guanylate cyclase C and/or a pertussis toxin-sensitive G protein in human proximal tubule cells. Sindiće, A., Başoglu, C., Cerçi, A., Hirsch, J.R., Potthast, R., Kuhn, M., Ghanekar, Y., Visweswariah, S.S., Schlatter, E. J. Biol. Chem. (2002) [Pubmed]
  4. Cellular effects of guanylin and uroguanylin. Sindić, A., Schlatter, E. J. Am. Soc. Nephrol. (2006) [Pubmed]
  5. Cloning and mRNA expression of guanylin, uroguanylin, and guanylyl cyclase C in the Spinifex hopping mouse, Notomys alexis. Donald, J.A., Bartolo, R.C. Gen. Comp. Endocrinol. (2003) [Pubmed]
  6. Increases in guanylin and uroguanylin in a mouse model of osmotic diarrhea are guanylate cyclase C-independent. Steinbrecher, K.A., Mann, E.A., Giannella, R.A., Cohen, M.B. Gastroenterology (2001) [Pubmed]
  7. Tyrosine phosphorylation of the human guanylyl cyclase C receptor. Bhandari, R., Mathew, R., Vijayachandra, K., Visweswariah, S. J. Biosci. (2000) [Pubmed]
  8. Guanylin and uroguanylin induce natriuresis in mice lacking guanylyl cyclase-C receptor. Carrithers, S.L., Ott, C.E., Hill, M.J., Johnson, B.R., Cai, W., Chang, J.J., Shah, R.G., Sun, C., Mann, E.A., Fonteles, M.C., Forte, L.R., Jackson, B.A., Giannella, R.A., Greenberg, R.N. Kidney Int. (2004) [Pubmed]
  9. The guanylin/STa receptor is expressed in crypts and apical epithelium throughout the mouse intestine. Swenson, E.S., Mann, E.A., Jump, M.L., Witte, D.P., Giannella, R.A. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  10. In vitro and in vivo evaluation of 177Lu- and 90Y-labeled E. coli heat-stable enterotoxin for specific targeting of uroguanylin receptors on human colon cancers. Giblin, M.F., Sieckman, G.L., Shelton, T.D., Hoffman, T.J., Forte, L.R., Volkert, W.A. Nucl. Med. Biol. (2006) [Pubmed]
  11. Guanylin peptides: cyclic GMP signaling mechanisms. Forte, L.R., Freeman, R.H., Krause, W.J., London, R.M. Braz. J. Med. Biol. Res. (1999) [Pubmed]
  12. In vitro and in vivo Evaluation of (111)In-labeled E. coli Heat-Stable Enterotoxin Analogs for Specific Targeting of Human Breast Cancers. Giblin, M.F., Gali, H., Sieckman, G.L., Owen, N.K., Hoffman, T.J., Volkert, W.A., Forte, L.R. Breast Cancer Res. Treat. (2006) [Pubmed]
  13. Cell line-specific transcriptional activation of the promoter of the human guanylyl cyclase C/heat-stable enterotoxin/receptor gene. Mann, E.A., Jump, M.L., Glenella, R.A. Biochim. Biophys. Acta (1996) [Pubmed]
  14. High salt intake increases uroguanylin expression in mouse kidney. Potthast, R., Ehler, E., Scheving, L.A., Sindic, A., Schlatter, E., Kuhn, M. Endocrinology (2001) [Pubmed]
  15. A role for guanylate cyclase C in acid-stimulated duodenal mucosal bicarbonate secretion. Rao, S.P., Sellers, Z., Crombie, D.L., Hogan, D.L., Mann, E.A., Childs, D., Keely, S., Sheil-Puopolo, M., Giannella, R.A., Barrett, K.E., Isenberg, J.I., Pratha, V.S. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  16. In vivo imaging of human colon cancer xenografts in immunodeficient mice using a guanylyl cyclase C--specific ligand. Wolfe, H.R., Mendizabal, M., Lleong, E., Cuthbertson, A., Desai, V., Pullan, S., Fujii, D.K., Morrison, M., Pither, R., Waldman, S.A. J. Nucl. Med. (2002) [Pubmed]
  17. Guanylyl cyclase C as a reliable immunohistochemical marker and its ligand Escherichia coli heat-stable enterotoxin as a potential protein-delivering vehicle for colorectal cancer cells. Buc, E., Vartanian, M.D., Darcha, C., Déchelotte, P., Pezet, D. Eur. J. Cancer (2005) [Pubmed]
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