PRKG is activated by binding to high levels of cGMP in the absence of WNT signaling

Stable Identifier
Reaction [binding]
Homo sapiens
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Active PKG homodimers restrict Ca2+ release in the absence of stimulation by phosphorylating a component of the IP3 receptor complex. PKG homodimers are activated at high (sub- to micromolar) concentrations of cGMP. Upon binding of cGMP to the high and low affinity sites in the regulatory domain, an allosteric change in secondary structure makes the catalytic site accessible to substrate (reviewed in Hoffman, 2005). WNT5A signaling through FZD2 in mouse F9 teratocarcinoma cells results in a PDE6-dependent decrease in cGMP levels. Under low cGMP conditions, the N-terminal domain of PKG occludes the catalytic site, reducing PKG activity and promoting Ca2+ release through the IP3 receptor (Ahumada et al, 2002; Ma and Yang, 2006).

Literature References
PubMed ID Title Journal Year
15545263 The biology of cyclic GMP-dependent protein kinases

Hofmann, F

J Biol Chem 2005
12471263 Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP

Wang, HY, Liu, X, Slusarski, DC, Malbon, CC, Ahumada, A, Moon, RT

Science 2002
16920709 Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/cGMP/Ca2+ pathway

Wang, HY, Ma, L

J. Biol. Chem. 2006
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