三种人类Dishevelled (DVL)蛋白在WNT信号级联的转导中起着中心和重叠的作用(Lee et al ., 2008;Gao and Chen, 2010)。DVL的活性是由磷酸化调控的,尽管细节尚未完全清楚。即使在没有WNT刺激的情况下,DVL也可能作为一种磷蛋白存在,并在配体结合后进一步磷酸化。据报道,酪蛋白激酶1epsilon (CSNK1E)、酪蛋白激酶2 (CSNK2)和PAR1均可使DVL磷酸化(Willert et al ., 1997;Sun et al, 2001;Cong等,2004;Ossipova等人,2005)。通路激活后,磷酸化的DVL通过DVL PDZ结构域和FZD KTxxxW motif之间的相互作用转移到质膜上(Wong et al ., 2003;Umbhauer等,2000; Kikuchi et al, 2011). At the plasma membrane, DVL is believed to oligomerize through its DIX domain, providing a platform for AXIN recruitment; recruitment of AXIN is also facilitated by interaction with LRP (Schwarz-Romond et al, 2007; Mao et al, 2001). DVL interacts with phosphatidylinositol-4-kinase type II (PI4KII) and phophatidylinositol-4-phosphate 5-kinase type I (PIP5KI) to promote formation of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the membrane, which is required for the clustering and phosphorylation of LRP6 and the recruitment of AXIN (Pan et al, 2008; Qin et al, 2009).