Hh信号促进SMO激活下游纤毛中GLI:SUFU复合物的解离(Humke et al .， 2010;图卡钦斯基等人，2010)。这似乎将转录因子从部分加工/降解途径转移，并允许全长形式转移到细胞核，在那里它们转化为不稳定的转录激活因子(Humke et al, 2010;图卡钦斯基等人，2010;Pan et al .， 2006;Kim等人，2009)。Hh信号是如何从SMO传递来促进GLI:SUFU复合体的解离的，目前还不清楚，但这可能与通路刺激后cAMP水平降低导致PKA活性的变化有关。(图卡钦斯基等人，2010;Wen et al, 2010;Tuson等人，2011年; Barzi et al, 2010; reviewed in Briscoe and Therond, 2013). GPR161, which localizes to the cilium in a TULP3-dependent manner and which increases cAMP levels in the absence of ligand, is cleared from the cilium upon pathway activation, and deletion of GPR161 increases Hh-dependent signaling (Mukhopadhyay et al, 2010; Mukhopadhyay et al, 2013). These data suggest that removal of ciliary GPR161 upon Hh stimulation may contribute to pathway activity by downregulating PKA activity through cAMP levels (reviewed in Mukhopadhyay and Rohatgi, 2014).