p-DVL2 recruits AP-2 and beta-arrestin 2 to promote clathrin-mediated endocytosis

Stable Identifier
R-HSA-5138433
Type
Reaction [binding]
Species
Homo sapiens
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Evidence suggests that FZD4 is endocytosed in a clathrin- and AP-2-dependent manner upon stimulation with WNT5A. Direct interactions have been demonstrated between DVL2 and the AP-2 component mu 2 mediated by simultaneous interaction with the DEP domain and a tetrapeptide motif YHEL of DVL2. Mutation of these regions abrogates FZD4 internalization and PCP signaling (Yu et al, 2007; Yu et al, 2010). DVL2 also interacts with beta-arrestin2 (ARBB2) in a PKC-dependent manner, and in vitro phosphorylation of DVL2 by PKC enhances the interaction between DVL2 and ARBB2 as assessed by co-immunoprecipitation (Chen et al, 2003). There is conflicting evidence on the requirement for ARBB2 for the internalization of FZD4 upon WNT5A signaling, however (Chen et al, 2003; Yu et al, 2007).

Literature References
PubMed ID Title Journal Year
12958364 Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4

Chen, W, ten Berge, D, Brown, J, Ahn, S, Hu, LA, Miller, WE, Caron, MG, Barak, LS, Nusse, R, Lefkowitz, RJ

Science 2003
17199046 Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signaling

Yu, A, Rual, JF, Tamai, K, Harada, Y, Vidal, M, He, X, Kirchhausen, T

Dev. Cell 2007
20947020 Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling

Yu, A, Xing, Y, Harrison, SC, Kirchhausen, T

Structure 2010
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