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Negative regulation of TCF-dependent signaling by WNT ligand antagonists

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-3772470

PubChem

R-HSA-3772470

Description

Several unrelated families of secreted proteins antagonize WNT signaling. Secreted frizzled-related proteins (sFRPs) have a cysteine rich domain (CRD) that is also found in FZD and ROR receptors, while WNT inhibitory factor (WIF) proteins contain a WIF domain also present in the WNT-receptor RYK. Both these classes of secreted WNT antagonists inhibit signaling by binding to WNTs and preventing their interaction with the FZD receptors. sFRPs may also able to bind the receptors, blocking ligand binding (Bafico et al, 1999; reviewed in Kawano and Kypta, 2003). The interaction of WIF and sFRPs with WNT ligand may also play a role in regulating WNT diffusion and gradient formation (reviewed in Boloventa et al, 2008).

Dickkopf (DKK) and Sclerostin (SOST) family members, in contrast, antagonize WNT signaling by binding to LRP5/6. There are four DKK family members in vertebrates; the closely related DKK1, 2 and 4 proteins have been shown to have roles in WNT signaling, while the more divergent DKK3 appears not to (Glinka et al, 1998; Fedi et al, 1999; Mao et al, 2001; Semenov et al, 2001; reviewed in Niehrs, 2006). Secreted DKK proteins bind to LRP6 in conjunction with the single-pass transmembrane proteins Kremen 1 and 2, and this interaction is thought to disrupt the WNT-induced FZD-LRP5/6 complex. In some cases, DKK2 has also been shown to function as a WNT agonist (reviewed in N (reviewed in Niehrs, 2006).
Like DKK proteins, SOST binds LRP5/6 and disrupts WNT-dependent receptor activation (Semenov et al, 2005).

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 13 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O14904	Protein Wnt-9a	WNT14 WNT9A	view
O75197	Low-density lipoprotein receptor-related protein 5	LR3 LRP5 LRP7	view
O75581	Low-density lipoprotein receptor-related protein 6	LRP6	view
O94907	Dickkopf-related protein 1	DKK1 UNQ492/PRO1008	view
P41221	Protein Wnt-5a	WNT5A	view
P56704	Protein Wnt-3a	WNT3A	view
P56705	Protein Wnt-4	UNQ426/PRO864 WNT4	view
Q8N474	Secreted frizzled-related protein 1	FRP FRP1 SARP2 SFRP1	view
Q8NCW0	Kremen protein 2	KREMEN2 KRM2	view
Q96MU8	Kremen protein 1	KREMEN KREMEN1 KRM1	view

Displaying 1 entry
GlyCosmos Lectin	UniProt ID	Lectin Name	Pathway Viewer
GL_001829	Q9BQB4	Sclerostin	view

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