Reactome | ZNRF3,RNF43 binds the FZD:LRP5/6 receptor complex

ZNRF3,RNF43 binds the FZD:LRP5/6 receptor complex

Stable Identifier

R-HSA-4641249

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

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ZNRF3,RNF43 binds the FZD:LRP5/6 receptor complex

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ZNFR3 and RNF43 are plasma membrane E3 RING domain ubiquitin ligases that have been shown to ubiquitinate FZD proteins to promote their downregulation (Hao et al, 2012). Inhibition of ZNRF3 or RNF43 increases the protein level of FZD and LRP6 at the plasma membrane, and stably expressed ZNRF3 can be co-immunoprecipitated with endogenous LRP6 and FZD6 (Hao et al, 2012; Jiang et al 2013). Turnover of the LRP6 and FZD receptors appears to be regulated by multiubiquitination and is abrogated upon treatment with lysosomal inhibitors (Mukai et al, 2010).

Literature References

PubMed ID	Title	Journal	Year
20495530	Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt Mukai, A, Yamamoto-Hino, M, Awano, W, Watanabe, W, Komada, M, Goto, S	EMBO J.	2010
22575959	ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner Hao, HX, Xie, Y, Zhang, Y, Charlat, O, Oster, E, Avello, M, Lei, H, Mickanin, C, Liu, D, Ruffner, H, Mao, X, Ma, Q, Zamponi, R, Bouwmeester, T, Finan, PM, Kirschner, MW, Porter, JA, Serluca, FC, Cong, F	Nature	2012
23847203	Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma Jiang, X, Hao, HX, Growney, JD, Woolfenden, S, Bottiglio, C, Ng, N, Lu, B, Hsieh, MH, Bagdasarian, L, Meyer, R, Smith, TR, Avello, M, Charlat, O, Xie, Y, Porter, JA, Pan, S, Liu, J, McLaughlin, ME, Cong, F	Proc. Natl. Acad. Sci. U.S.A.	2013