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

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

Stable Identifier

R-HSA-4551453

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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

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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