Reactome | G alpha t2 binds and activates PDE6

G alpha t2 binds and activates PDE6

Stable Identifier

R-HSA-4086393

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Signaling by WNT5A and FZD2 activates PDE6 through G protein alpha subunit t2 (Liu et al, 1999; Ahumada et al, 2002). The discovery that G alpha t2 is involved in WNT:Ca2+ signaling was surprising, as this G protein subunit is best characterized for its role in visual transduction and its expression in vertebrates is almost exclusively restricted to the visual pathway (reviewed in Wang et al, 2004). Recent work in the WNT field has shown that a pathway similar to the visual transduction cascade exists in the mouse F9 teratocarcinoma cell line, CHO cells, zebrafish embryos as well as in a number of human cancer cell lines (Liu et al, 1999; Ahumada et al, 2002). PDE6 is a tetramer of two catalytic subunits, alpha and beta, held in an inactive conformation by two regulatory gamma subunits. Recruitment and binding with G alpha t2 relaxes the inhibitory effect of PDE6gamma and allows activation of the catalytic subunits (reviewed in Wensel, 2008). Activation of PDE6 in the WNT pathway may also depend on p38 MAPK (Ma and Wang, 2007).

Literature References

PubMed ID	Title	Journal	Year
18456304	Signal transducing membrane complexes of photoreceptor outer segments Wensel, TG	Vision Res.	2008
15494017	PDE6 is an effector for the Wnt/Ca2+/cGMP-signalling pathway in development Wang, H, Lee, Y, Malbon, CC	Biochem. Soc. Trans.	2004
17684012	Mitogen-activated protein kinase p38 regulates the Wnt/cyclic GMP/Ca2+ non-canonical pathway Ma, L, Wang, HY	J. Biol. Chem.	2007
10588714	Activation of a frizzled-2/beta-adrenergic receptor chimera promotes Wnt signaling and differentiation of mouse F9 teratocarcinoma cells via Galphao and Galphat Liu, X, Liu, T, Slusarski, DC, Yang-Snyder, J, Malbon, CC, Moon, RT, Wang, H	Proc. Natl. Acad. Sci. U.S.A.	1999
12471263	Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP Ahumada, A, Slusarski, DC, Liu, X, Moon, RT, Malbon, CC, Wang, HY	Science	2002