GSK-3𝜷: A Bifunctional Role in Cell Death Pathways

Table 3

List of known positive regulators of GSK-3β.

Activator	Activation potency	Mode of activation	Notes
Celecoxib	IC50 = 3.5 μM	Inhibits PDK phosphorylation of Akt	COX-2 inhibitor [100].
Staurosporine	IC50 = 0.22 μM	Inhibits PDK phosphorylation of Akt	General kinase inhibitor (including PKA/PKC) [101, 103, 104].
Trichostatin A	Unknown	Induces Akt dephosphorylation	HDAC inhibitor acts through PP1 [105].
Curcumin	Unknown	Akt dephosphorylation	Direct target not known [102].
Akt/protein kinase B; signaling inhibitor-2 (API-2)	Unknown	Suppresses Akt kinase activity and activation	Does not affect upstream Akt activators [106].
Wortmannin	IC50 = 5 nM	Inhibits PI3-Kinase	Indirect effect on GSK-3𝛽 [97, 98].
LY294002	IC50 = 1.4 μM	Inhibits PI3-Kinase	Likely affects ATP binding to kinase [98, 99].
Rapamycin	Unknown	Potentially inhibits S6K1	mTOR pathway can also inhibit GSK3 [107, 108].
Differentiation-inducing; factors (DIFs)	Unknown	Enhances GSK-3β kinase activity and promotes nuclear localization	Reduces inhibitory phosphorylation and enhances activating phosphorylation [111, 112].
Retinoids	Unknown	Reduces inhibitory phosphorylation of GSK-3β	Promotes GSK-3β-dependent cyclin D1 degradation [80, 109].