Dvl proteins serve an important role in the regulation and initiation of Wnt signaling. The upregulation of Dvl has been correlated with cancers.108 109 The Dvl proteins may not only interact with FzRs to initiate activation of the TCF-LEF transcription factors, they may also activate RhoA. In addition, Dvl proteins may also participate in the regulation of FzR-mediated signaling. Dvl proteins may be phosphorylated by protein kinase C (PKC), allowing the recruitment of p-arrestin-2 to the plasma membrane.110 p-arrestin is an adaptor protein that, when bound to the receptor, targets receptors to endocytosis that may result in the routing of receptors to lysosomes for receptor degradation.
In addition to p-arrestin-2, p-arrestin-1 has been shown to bind to both Dvl-1 and Dvl-2. Phosphorylation of Dvl enhances this binding, and the coexpression of p-arrestin-1 with Dvl-1 or Dvl-2 synergistically enhances the activity of the LEF transcription factor,111 suggesting that p-arrestin-1 may also serve as an adapter for FzRs. In addition to serving as adapter proteins, arrestins may serve as scaffolds linking GPCRs to other signaling proteins such as the src family of kinases and members of the mitogen-activated protein kinase cascade.
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