Casein kinase 1 alpha and gamma isoforms (CK1α/γ)

Casein kinase 1 (CK1) alpha and gamma isoforms are members of a highly conserved family of serine/threonine protein kinases that serve as essential regulators of diverse cellular signaling pathways. CK1 alpha (CSNK1A1) is a key component of the beta-catenin destruction complex, where it phosphorylates beta-catenin to trigger its degradation, thereby acting as a negative regulator of canonical Wnt signaling (1.1.2, 1.4.1). In contrast, CK1 gamma isoforms (CSNK1G1, CSNK1G2, CSNK1G3) are membrane-associated kinases that typically promote Wnt signaling by phosphorylating LRP6 (1.3.2, 1.4.5). Beyond Wnt signaling, these isoforms are involved in Hedgehog signaling, DNA repair, and the regulation of the tumor suppressor p53 (1.3.5, 1.4.1). Dysregulation of these kinases is implicated in the pathogenesis of various cancers, particularly hematological malignancies like myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), as well as solid tumors like colorectal cancer (1.1.2, 1.4.3). Therapeutic strategies include the use of molecular glues like lenalidomide, which induces the degradation of CK1 alpha to treat del(5q) MDS, and small molecule inhibitors like BTX-A51 currently in clinical development for AML (1.3.3, 1.4.1).

Other names

CSNK1A1CSNK1G1CSNK1G2CSNK1G3CK1 alphaCK1 gammaCasein kinase 1 alpha 1Casein kinase 1 gamma 1Casein kinase 1 gamma 2Casein kinase 1 gamma 3

Targeted protein degradation (molecular glue-induced ubiquitination), ATP-competitive kinase inhibition, and allosteric activation.