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. Author manuscript; available in PMC: 2016 Apr 1.
Published in final edited form as: Pharmacol Ther. 2014 Nov 27;0:114–131. doi: 10.1016/j.pharmthera.2014.11.016

Figure 4. GSK3 interactions with G protein-coupled receptor-induced signaling mechanisms.

Figure 4

Dopaminergic D2 receptor activation induces the association of β-arrestin, Akt, GSK3, and protein phosphatase 2A (PP2A). This facilitates PP2A-mediated dephosphorylation of Akt and GSK3, deactivating Akt and activating GSK3. GSK3 facilitates the formation of this complex, providing a mechanism for GSK3 to induce its own activation. Self-activation by GSK3 is also exemplified by its phosphorylation of the protein phosphatase 1 (PP1) inhibitor I-2, resulting in increased PP1 activity, which dephosphorylates the inhibitory serine-phosphorylation of GSK3 to increase GSK3 activity. Serotonin (5HT) 2A receptor activation reduces serine-phosphorylation of GSK3, thereby increasing its activity. 5HT1A and cholinergic muscarinic receptor activation increase the inhibitory serine-phosphorylation of GSK3. GSK3 promotes 5HT1B receptor-mediated activation of the heterotrimeric G protein, Gi, which inhibits cyclic AMP production.