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 .[ 5] [ 6]
Guanylyl cyclase is an enzyme found in the luminal aspect of intestinal epithelium and dopamine neurons in the brain .[ 7] 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 .[ 8] 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 .
References
^ a b c GRCh38: Ensembl release 89: ENSG00000070019 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042638 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Entrez Gene: guanylate cyclase 2C (heat stable enterotoxin receptor)" .^ Mann EA, Swenson ES, Copeland NG, Gilbert DJ, Jenkins NA, Taguchi T, Testa JR, Giannella RA (June 1996). "Localization of the guanylyl cyclase C gene to mouse chromosome 6 and human chromosome 12p12". Genomics . 34 (2): 265–7. doi :10.1006/geno.1996.0284 . PMID 8661067 . ^ Intestinal Protein May Have Role in ADHD, Other Neurological Disorders. ScienceDaily (Aug. 11, 2011) [1]
^ Weiglmeier PR, Rösch P, Berkner H (August 2010). "Cure and Curse: E. coli Heat-Stable Enterotoxin and Its Receptor Guanylyl Cyclase C" . Toxins . 2 (9): 2213–2229. doi :10.3390/toxins2092213 PMC 3153297 PMID 22069681 .
Further reading
Schulz S, Hyslop T, Haaf J, et al. (2006). "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. doi :10.1158/1078-0432.CCR-06-0865 PMID 16899600 . Park J, Schulz S, Haaf J, et al. (2002). "Ectopic expression of guanylyl cyclase C in adenocarcinomas of the esophagus and stomach". Cancer Epidemiol. Biomarkers Prev . 11 (8): 739–44. PMID 12163327 . Tien YW, Lee PH, Hu RH, et al. (2003). "The role of gelatinase in hepatic metastasis of colorectal cancer". Clin. Cancer Res . 9 (13): 4891–6. PMID 14581363 . Basu N, Bhandari R, Natarajan VT, Visweswariah SS (2009). "Cross talk between receptor guanylyl cyclase C and c-src tyrosine kinase regulates colon cancer cell cytostasis" . Mol. Cell. Biol . 29 (19): 5277–89. doi :10.1128/MCB.00001-09 . PMC 2747985 PMID 19620276 . Mann EA, Steinbrecher KA, Stroup C, et al. (2005). "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. doi :10.1002/ijc.21119 PMID 15825168 . S2CID 28833622 . Saha S, Biswas KH, Kondapalli C, et al. (2009). "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. doi :10.1074/jbc.M109.020032 PMC 2786029 PMID 19648115 . Bhandari R, Srinivasan N, Mahaboobi M, et al. (2001). "Functional inactivation of the human guanylyl cyclase C receptor: modeling and mutation of the protein kinase-like domain". Biochemistry . 40 (31): 9196–206. doi :10.1021/bi002595g . PMID 11478887 . Sindiće A, Başoglu C, Cerçi A, et al. (2002). "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. doi :10.1074/jbc.M110627200 PMID 11889121 . Jaleel M, London RM, Eber SL, et al. (2002). "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. doi :10.1095/biolreprod.102.006445 PMID 12444076 . Mejia A, Schulz S, Hyslop T, et al. (2009). "GUCY2C reverse transcriptase PCR to stage pN0 colorectal cancer patients" . Expert Rev. Mol. Diagn . 9 (8): 777–85. doi :10.1586/erm.09.67 . PMC 2810399 PMID 19895223 . Scott RO, Thelin WR, Milgram SL (2002). "A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor" . J. Biol. Chem . 277 (25): 22934–41. doi :10.1074/jbc.M202434200 PMID 11950846 . Ghanekar Y, Chandrashaker A, Tatu U, Visweswariah SS (2004). "Glycosylation of the receptor guanylate cyclase C: role in ligand binding and catalytic activity" . Biochem. J . 379 (Pt 3): 653–63. doi :10.1042/BJ20040001 . PMC 1224121 PMID 14748740 . Kulaksiz H, Cetin Y (2001). "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. doi :10.1677/joe.0.1700267 PMID 11431160 . Debruyne PR, Witek M, Gong L, et al. (2006). "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. 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 . Selvaraj NG, Prasad R, Goldstein JL, Rao MC (2000). "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. doi :10.1016/s0167-4889(00)00075-6 PMID 11042348 . Ciocca V, Bombonati A, Palazzo JP, et al. (2009). "Guanylyl cyclase C is a specific marker for differentiating primary and metastatic ovarian mucinous neoplasms" . Histopathology . 55 (2): 182–8. doi :10.1111/j.1365-2559.2009.03358.x . PMC 3140017 PMID 19694825 . Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "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. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags" . Proc. Natl. Acad. Sci. U.S.A . 97 (7): 3491–6. Bibcode :2000PNAS...97.3491D . doi :10.1073/pnas.97.7.3491 PMC 16267 PMID 10737800 .
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Activity Regulation Classification Kinetics Types
