Meta-Biol

• Pathways

Initial activation of SMO in response to HH occurs with the CSNK1A1-mediated phosphorylation of serine and threonine residues in the C-terminal tail. While many potential CSNK1A1 target residues have been identified in in vitro assays, residues S588, S590, T593 and S595 in the S0 region appear to be the most critical for function (Chen et al, 2011). Initial phosphorylation increases the affinity of the C-terminal tail for both CSNK1A1 and ADRBK1/GRK2, establishing a positive feedback mechanism that promotes further phosphorylation. CSNK1A1 and ADRBK1-mediated phosphorylation is thought to promote an open, activated conformation of the C-terminal tails, analogous to that in Drosophila Smo upon pathway activation (Chen et al, 2011; Chen et al, 2010; Zhao et al, 2007).