Biology:Guanylate cyclase 2C

Generic protein structure example

Guanylate cyclase 2C, also known as guanylyl cyclase C (GC-C), intestinal guanylate cyclase, guanylate cyclase-C receptor, or the heat-stable enterotoxin receptor (hSTAR) is an enzyme that in humans is encoded by the GUCY2C gene.

Guanylyl cyclase is an enzyme found in the luminal aspect of intestinal epithelium and dopamine neurons in the brain. The receptor has an extracellular ligand-binding domain, a single transmembrane region, a region with sequence similar to that of protein kinases, and a C-terminal guanylate cyclase domain. Tyrosine kinase activity mediates the GC-C signaling pathway within the cell.

Functions

GC-C is a key receptor for heat-stable enterotoxins that are responsible for acute secretory diarrhea. Heat-stable enterotoxins are produced by pathogens such as Escherichia coli. Knockout mice deficient in the GC-C gene do not show secretory diarrhea on infection with E. coli, though they do with cholera toxin. This demonstrates the specificity of the GC-C receptor.

In medicine

Guanylate cyclase 2C is the target of linaclotide and plecanatide, oligopeptide agonists used for the treatment of chronic constipation.

Further reading

• "A validated quantitative assay to detect occult micrometastases by reverse transcriptase-polymerase chain reaction of guanylyl cyclase C in patients with colorectal cancer.". Clin. Cancer Res. 12 (15): 4545–52. 2006. doi:10.1158/1078-0432.CCR-06-0865. PMID 16899600. 
• "Ectopic expression of guanylyl cyclase C in adenocarcinomas of the esophagus and stomach.". Cancer Epidemiol. Biomarkers Prev. 11 (8): 739–44. 2002. PMID 12163327. 
• "The role of gelatinase in hepatic metastasis of colorectal cancer.". Clin. Cancer Res. 9 (13): 4891–6. 2003. PMID 14581363. 
• "Cross talk between receptor guanylyl cyclase C and c-src tyrosine kinase regulates colon cancer cell cytostasis.". Mol. Cell. Biol. 29 (19): 5277–89. 2009. doi:10.1128/MCB.00001-09. PMID 19620276. 
• "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.". Int. J. Cancer 116 (4): 500–5. 2005. doi:10.1002/ijc.21119. PMID 15825168. 
• "The linker region in receptor guanylyl cyclases is a key regulatory module: mutational analysis of guanylyl cyclase C.". J. Biol. Chem. 284 (40): 27135–45. 2009. doi:10.1074/jbc.M109.020032. PMID 19648115. 
• "Functional inactivation of the human guanylyl cyclase C receptor: modeling and mutation of the protein kinase-like domain.". Biochemistry 40 (31): 9196–206. 2001. doi:10.1021/bi002595g. PMID 11478887. 
• "Guanylin, uroguanylin, and heat-stable euterotoxin activate guanylate cyclase C and/or a pertussis toxin-sensitive G protein in human proximal tubule cells.". J. Biol. Chem. 277 (20): 17758–64. 2002. doi:10.1074/jbc.M110627200. PMID 11889121. 
• "Expression of the receptor guanylyl cyclase C and its ligands in reproductive tissues of the rat: a potential role for a novel signaling pathway in the epididymis.". Biol. Reprod. 67 (6): 1975–80. 2002. doi:10.1095/biolreprod.102.006445. PMID 12444076. 
• "GUCY2C reverse transcriptase PCR to stage pN0 colorectal cancer patients.". Expert Rev. Mol. Diagn. 9 (8): 777–85. 2009. doi:10.1586/erm.09.67. PMID 19895223. 
• "A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor.". J. Biol. Chem. 277 (25): 22934–41. 2002. doi:10.1074/jbc.M202434200. PMID 11950846. 
• "Glycosylation of the receptor guanylate cyclase C: role in ligand binding and catalytic activity.". Biochem. J. 379 (Pt 3): 653–63. 2004. doi:10.1042/BJ20040001. PMID 14748740. 
• "Uroguanylin and guanylate cyclase C in the human pancreas: expression and mutuality of ligand/receptor localization as indicators of intercellular paracrine signaling pathways.". J. Endocrinol. 170 (1): 267–75. 2001. doi:10.1677/joe.0.1700267. PMID 11431160. 
• "Bile acids induce ectopic expression of intestinal guanylyl cyclase C Through nuclear factor-kappaB and Cdx2 in human esophageal cells.". Gastroenterology 130 (4): 1191–206. 2006. doi:10.1053/j.gastro.2005.12.032. PMID 16618413. 
• Singh R (2003). "Interaction of guanylyl cyclase C with SH3 domain of Src tyrosine kinase. Yet another mechanism for desensitization.". J. Biol. Chem. 278 (27): 24342–9. doi:10.1074/jbc.M301153200. PMID 12649275. 
• "Evidence for the presence of cGMP-dependent protein kinase-II in human distal colon and in T84, the colonic cell line.". Biochim. Biophys. Acta 1498 (1): 32–43. 2000. doi:10.1016/s0167-4889(00)00075-6. PMID 11042348. 
• "Guanylyl cyclase C is a specific marker for differentiating primary and metastatic ovarian mucinous neoplasms.". Histopathology 55 (2): 182–8. 2009. doi:10.1111/j.1365-2559.2009.03358.x. PMID 19694825. 
• "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. 2000. doi:10.1073/pnas.97.7.3491. PMID 10737800. Bibcode: 2000PNAS...97.3491D. 

External links

• GCC testing for colorectal cancer staging
• GC-C knock-out mice
• guanyl+cyclase-C+receptor at the US National Library of Medicine Medical Subject Headings (MeSH)