Meta-Biol

• Pathways

ADRBK1 phosphorylates the SMO C-terminal tail after initial phosphorylation by CSNK1A1. Phosphorylation promotes an open, activated conformation of the C-terminal tails, allowing an intramolecular interaction between tails of adjacent monomers in the SMO dimer. This Hh-dependent conformational change is required for downstream signal propagation (Chen et al, 2011; Chen et al, 2010; Zhao et al, 2007; Meloni et al, 2006; Philipp et al, 2008; reviewed in Briscoe and Therond, 2013). In Drosophila, Smo C-terminal tail phosphorylation promotes an association with the Hedgehog signaling complex (HSC) through interaction with the scaffolding kinesin-2 like protein Cos2, and ultimately results in the release of full-length Ci from the complex (Zhang et al, 2005; Ogden et al, 2003; Lum et al, 2003; reviewed in Mukhopadhyay and Rohatgi, 2014). How Hh signal is transmitted from activated SMO to downstream components in vertebrate cells is not fully established