From Wikipedia, the free encyclopedia
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] 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 .
[8] 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 .
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 .
External links
Activity Regulation Classification Kinetics Types