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Background Guanylyl cyclase C (GC-C) is a receptor expressed in intestinal epithelial cells and activation of GCC by its ligands elevates intracellular cGMP which results in an inhibition of cell proliferation [1]. Multiple regulatory mechanisms operate in GC-C to modulate its activity, and include ligand binding to the extracellular domain, ATP binding to the kinase homology domain and additional structural features that link the kinase homology domain to the C-terminal guanylyl cyclase domain [2]. The persistent expression of GC-C in colorectal carcinomas and occult metastases makes it a marker for malignancy.

Signaling via guanylyl cyclase C: cGMP, Src and p21