ADRBK1 phosphorylates SMO dimer

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

ADRBK1在CSNK1A1初步磷酸化后，对SMO的C端尾巴进行磷酸化。磷酸化作用促进C端尾巴形成开放、激活的构象，从而使相邻单体在SMO二聚体中的尾巴之间发生分子内相互作用。这种Hh依赖性的构象变化对于下游信号传导至关重要（Chen等，2011；Chen等，2010；Zhao等，2007；Meloni等，2006；Philipp等，2008；参见Briscoe和Therond，2013年的综述）。在果蝇中，Smo C端尾巴的磷酸化通过与其骨架肌球蛋白-2样蛋白Cos2相互作用，促进与Hedgehog信号复合物（HSC）的结合，并最终导致从复合物中释放出全长Ci（Zhang等，2005；Ogden等，2003；Lum等，2003；参见Mukhopadhyay和Rohatgi，2014年的综述）。在脊椎细胞中，Hh信号如何从激活的SMO传递至下游组分尚无定论。