Figure 5.

Schematic representation of the Escherichia coli thermostable enterotoxin (STa), a hormone-like toxin. STa binds to guanylyl cyclase C (GC-C) and induces GC-C dimerization and activation through conformational change in the inhibitor kinase homology domain. Increased level of cGMP activates cGMP-dependent protein kinase II (PKGII) and subsequently the cystic fibrosis transmembrane conductance regulator (CFTR) channel. In addition, cGMP inhibits the phosphodiesterase 3 (PDE3) resulting in the accumulation of cAMP and subsequently, further activation of CFTR and inhibition of the Na⁺/H⁺-exchanger 3 channel (NHE3).