CRD motif and sFRPs influence on Wnt signaling (Danio rerio)

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1Activation by N-terminal CRD motifEnhanced signalingFz7 receptorLegend:EndocytosisRoaAWnt5adistinct non-canonical Wnt pathways papcrhoaaJNKRor2 receptorsFRP2distinct non-canonical Wnt pathways Activation by extracellular CRD motif Endocytosisdistinct non-canonical Wnt pathways papcpapcpapcpapcpapcpapcEndocytosisrhoabrhoacRoaAJNKJNKFz7aFz7bFz7 receptorFz7 receptorRor2 receptorsFRP2Ror2 receptorFz7 receptor


Wnt signaling plays a crucial role in embryogenesis as well as in adult stem cell regulation and cancer.

The Wnt signaling cascade is initiated by binding of secreted Wnt proteins to seven-pass transmembrane Fz receptors and diverse co-receptors. The extracellular CRD of Fz family members thereby serves as a highly conserved binding site for Wnt ligands.

When expressed alone, Fz7 or Ror2 receptors activate distinct non-canonical Wnt pathways stimulated by Wnt5a. When sFRP2 is present, Fz7 receptor endocytosis is prevented, and Fz7 signaling is inhibited, whereas Ror2 signaling is enhanced indicated by stabilized Wnt5a-Ror2 membrane complexes.

When both receptors are present in the same cell, the Ror2-CRD acts in a similar way as sFRP2, leading to increased Ror2 activation at the expense of Fz7 signaling.


Study conducted on wild-type zebrafish AB2O3.

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  1. Brinkmann EM, Mattes B, Kumar R, Hagemann AI, Gradl D, Scholpp S, Steinbeisser H, Kaufmann LT, Özbek S; ''Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation.''; J Biol Chem, 2016 PubMed Europe PMC Scholia


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96496view21:34, 15 March 2018DeSlChanged gene node to textlabel where needed, slight modification of title.
96495view21:32, 15 March 2018DeSlAdded more IDs
96494view21:16, 15 March 2018DeSlOntology Term : 'embryonic stem cell' added !
96492view21:11, 15 March 2018DeSlOntology Term : 'Wnt signaling pathway' added !
96491view21:11, 15 March 2018DeSlModified description
96489view21:08, 15 March 2018DeSlNew pathway

External references


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NameTypeDatabase referenceComment
Fz7aGeneProductENSDARG00000060004 (Ensembl)
Fz7bGeneProductENSDARG00000027589 (Ensembl)
JNKProteinF1R9P8 (Uniprot-TrEMBL) Choose ID here for "Jnk1/mapk8-associated membrane protein"
Ror2 receptorGeneProductENSDARG00000076227 (Ensembl) A single-pass transmembrane receptor tyrosine kinase and contains an N-terminal CRD that interacts with Wnt5a.
Wnt5aGeneProductENSDARG00000104973 (Ensembl)
distinct non-canonical Wnt pathways Pathway
papcProteinENSDARG00000102185 (Ensembl)
rhoaaGeneProductENSDARG00000026845 (Ensembl)
rhoabGeneProductENSDARG00000094673 (Ensembl)
rhoacGeneProductENSDARG00000099709 (Ensembl)
sFRP2GeneProductENSDARG00000070050 (Ensembl)

Annotated Interactions

No annotated interactions
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