Glycogen synthase kinase 3 beta (GSK3β) and Casein kinase 1 alpha (CK1α) (GSK3β, CK1α)

Glycogen synthase kinase 3 beta (GSK3β) and casein kinase 1 alpha (CK1α) are serine/threonine protein kinases—enzymes that act as phosphotransferases—central to the canonical Wnt/β-catenin signaling pathway. In the absence of Wnt signaling, they phosphorylate β-catenin within the destruction complex (which includes Axin and APC), marking β-catenin for ubiquitination and proteasomal degradation. Upon Wnt ligand binding to Frizzled and LRP5/6 receptors, recruitment and phosphorylation events alter the complex, suppressing GSK3β/CK1α action on β-catenin, thereby allowing β-catenin stabilization, nuclear translocation, and transactivation of Wnt-responsive genes crucial for proliferation, differentiation, development, and stem cell maintenance. Dysregulation of these kinases is strongly implicated in cancer and other diseases[1][2][4][5][7].

Other names

GSK-3βGlycogen synthase kinase 3 betaCasein kinase 1 alphaCK1α

Inhibition of β-catenin phosphorylation and degradation (GSK3β/CK1α inhibitors) Activation/suppression of downstream Wnt target gene transcription