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

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

Compartment

plasma membrane, cytosol

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

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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