Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q96S42 (nodal)
 22,877 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Frizzled proteins act as putative Wnt receptors and depending on Wnt/Frizzled interactions distinct intracellular pathways can be activated. The canonical Wnt pathway, triggered by Wnt-1-type ligands, is the best characterized and involves the activation of the cytoplasmic protein Dishevelled (Dsh). The Xenopus frizzled 7 receptor (Xfz7) can act in the canonical (Wnt-1-type) as well as in a non-canonical Wnt pathway which involves the activation of protein kinase C (PKC). In order to analyze the interaction between Xfz7 and Xdsh protein, we tested the effect of overexpression of Xfz7 on the subcellular distribution of Xdsh-myc protein. We demonstrate that Xfz7 can recruit Xdsh-myc to the plasma membrane and target genes of the Wnt-1-type pathway such as siamois and nodal related 3 (Xnr-3) are only activated in the presence of exogenous Xdsh-myc. Xfz7 in combination with Xwnt-8b, however, is able to induce siamois even in the absence of Xdsh-myc. Similar results were obtained after expression of Human frizzled 5 (Hfz5) together with Xwnt-5a but this receptor-ligand combination recruits Xdsh-myc only very poorly to the membrane. These results suggests that the endogenous Xdsh pool and exogenous Xdsh-myc differ in their ability to be recruited by Frizzled receptors.
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PMID:Interaction of Frizzled 7 and Dishevelled in Xenopus. 1090 85

Seven-transmembrane receptors of the frizzled family can interact with secreted Wnt ligands and transmit Wnt signals into the cell. Dependent on the ligand receptor combination, distinct Wnt pathways are activated. Xenopus frizzled 7 (Xfz7) and Xwnt-8b as well as Human frizzled 5 (Hfz5) and Xwnt-5a can act synergistically in the activation of Wnt/beta-catenin target genes siamois (Xsia) and nodal related 3 (Xnr3) and in the induction of ectopic axes in Xenopus embryos. In order to characterize the role of different protein domains of Xfz7 in Wnt/beta-catenin signaling, chimeric Xfz7/Hfz5 receptors were generated in which the extracellular (N5-TC7) or the intracellular domains (NT7-C5) between Xfz7 and Hfz5 were exchanged. We present evidence that the extracellular domain of Xfz7 can interact with Xwnt-5a and that the intracellular C-terminus can transmit a Wnt/beta-catenin signal. Despite these abilities, Xfz7 and Xwnt-5a do not act synergistically in the activation of Wnt/beta-catenin targets. This implies that the interaction of a frizzled receptor with different ligands can result in distinct cellular responses.
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PMID:Functional analysis of the Xenopus frizzled 7 protein domains using chimeric receptors. 1129 55