sFRP binds WNT3A and inhibits WNT:FZD binding

Stable Identifier
R-HSA-3772441
Type
Reaction [binding]
Species
Homo sapiens
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Mammalian genomes encode 5 secreted Frizzled related proteins (sFRPs) that are proposed to antagonize WNT signaling by binding directly to WNT ligands. Binding is mediated by a cysteine-rich-domain in the N-terminal that is homologous to the one found in FZD receptors and which is also found in the alternative WNT receptors ROR1 and ROR2 (reviewed in Kawano and Kupta, 2003; Boloventa et al, 2008). Direct binding of sFRP1, 2, 3 and 4 to Wnt3a has been demonstrated by surface plasmon resonance, but only sFRP1 and 2 were shown to inhibit Wtn3a-dependent signaling in mouse ES cells (Wawrzak et al, 2007). In addition to binding to WNT ligands, sFRPs are proposed to antagonize WNT signaling in a number of other ways. sFRPs have been shown to bind directly to FZD proteins by virtue of the CRDs: this interaction is postulated to block WNT signaling by inhibiting the WNT:FZD interaction (Bafico et al, 1999; Rodgriguez et al, 2005).

Literature References
PubMed ID Title Journal Year
12775774 Secreted antagonists of the Wnt signalling pathway

Kawano, Y, Kypta, R

J. Cell. Sci. 2003
18322270 Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease

Bovolenta, P, Esteve, P, Ruiz, JM, Cisneros, E, Lopez-Rios, J

J. Cell. Sci. 2008
16172602 SFRP1 regulates the growth of retinal ganglion cell axons through the Fz2 receptor

Rodriguez, J, Esteve, P, Weinl, C, Ruiz, JM, Fermin, Y, Trousse, F, Dwivedy, A, Holt, C, Bovolenta, P

Nat. Neurosci. 2005
10347172 Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling

Bafico, A, Gazit, A, Pramila, T, Finch, PW, Yaniv, A, Aaronson, SA

J. Biol. Chem. 1999
17462603 Wnt3a binds to several sFRPs in the nanomolar range

Wawrzak, D, M├ętioui, M, Willems, E, Hendrickx, M, de Genst, E, Leyns, L

Biochem. Biophys. Res. Commun. 2007
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