CK1 in Developmental Signaling: Hedgehog and Wnt

The casein kinase 1 (CK1) family of serine (Ser)/threonine (Thr) protein kinases participates in a myriad of cellular processes including developmental signaling. Hedgehog (Hh) and Wnt pathways are two major and evolutionarily conserved signaling pathways that control embryonic development and adult tissue homeostasis. Deregulation of these pathways leads to many human disorders including birth defects and cancer. Here, I review the role of CK1 in the regulation of Hh and Wnt signal transduction cascades from the membrane reception systems to the transcriptional effectors. In both Hh and Wnt pathways, multiple CK1 family members regulate signal transduction at several levels of the pathways and play either positive or negative roles depending on the signaling status, individual CK1 isoforms involved, and the specific substrates they phosphorylate. A common mechanism underlying the control of CK1-mediated phosphorylation of Hh and Wnt pathway components is the regulation of CK1/substrate interaction within large protein complexes. I will highlight this feature in the context of Hh signaling and draw interesting parallels between the Hh and Wnt pathways.