Although GSK3β can be phosphorylated at Ser9 by multiple kinases such as Akt, ERK and PKA, such a phosphorylation of GSK3β will only inactivate GSK3β (Li et al., 2000; Jo et al., 2011; Yamaguchi et al., 2012), and thus cannot explain an ethanol-induced activation of GSK3β. Ethanol-induced GSK3β activation may be explained by the decreased levels of inhibitory GSK3β phosphorylation at the Ser9 residue (Liu et al., 2009). Alternatively, GSK3β is also capable of being regulated by an activation pathway. Activation of GSK3β is accomplished by phosphorylation at tyrosine 216 (Tyr216), but whether ethanol can induce GSK3β phosphorylation at Tyr216 remains to be further determined.
