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; Bazhin et al, 2010). 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).