Guanylin is a peptide hormone activator of membrane-bound guanylate cyclase C (GC-C).1,2 It contains four cysteines that can form disulfide bridges leading to two possible isoforms, with the active form containing disulfide bridges between Cys4 and Cys12 and Cys7 and Cys15.1 Guanylin is found in epithelial cells of the small intestine where it activates GC-C to increase intestinal chloride and fluid secretion.2,3,4 Guanylin expression is reduced by 100- to 1,000-fold in greater than 85% of isolated tumors from patients with colorectal cancer compared with adjacent non-cancerous intestinal epithelial tissue.5
1.Nokihara, K., Wray, V., Ando, E., et al.Synthesis, solution structure, binding activity, and cGMP activation of human guanylin and its disulfide isomerRegul. Pept.70(2-3)111-120(1997) 2.de Sauvage, F.J., Keshav, S., Kuang, W.-J., et al.Precursor structure, expression, and tissue distribution of human guanylinProc. Natl. Acad. Sci. USA89(19)9089-9093(1992) 3.Hill, O., Kuhn, M., Zucht, H.-D., et al.Analysis of the human guanylin gene and the processing and cellular localization of the peptideProc. Natl. Acad. Sci. USA92(6)2046-2050(1995) 4.Forte, L.R., and Currie, M.G.Guanylin: A peptide regulator of epithelial transportFASEB J.9(8)643-650(1995) 5.Wilson, C., Lin, J.E., Snook, A.E., et al.The paracrine hormone for the GUCY2C tumor suppressor, guanylin, is universally lost in colorectal cancerCancer Epidemiol. Biomarkers Prev.23(11)2328-2337(2014)