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Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease

Autores

Bovolenta, Paola , Esteve, Pilar , Ruiz, Jose Maria , Cisneros, Elsa , LÓPEZ-RÍOS MORENO, JAVIER

Publicación externa

Si

Medio

J. Cell Sci.

Alcance

Review

Naturaleza

Científica

Cuartil JCR

Cuartil SJR

Impacto JCR

6.247

Impacto SJR

5.511

Fecha de publicacion

15/03/2008

ISI

000254660200002

Abstract

The secreted Frizzled-related proteins (SFRPs) are a family of soluble proteins that are structurally related to Frizzled (Fz) proteins, the serpentine receptors that mediate the extensively used cell-cell communication pathway involving Wnt signalling. Because of their homology with the Wnt-binding domain on the Fz receptors, SFRPs were immediately characterised as antagonists that bind to Wnt proteins to prevent signal activation. Since these initial studies, interest in the family of SFRPs has grown progressively, offering new perspectives on their function and mechanism of action in both development and disease. These studies indicate that SFRPs are not merely Wnt-binding proteins, but can also antagonise one another's activity, bind to Fz receptors and influence axon guidance, interfere with BMP signalling by acting as proteinase inhibitors, and interact with other receptors or matrix molecules. Furthermore, their expression is altered in different types of cancers, bone pathologies, retinal degeneration and hypophosphatemic diseases, indicating that their activity is fundamental for tissue homeostasis. Here we review some of the debated aspects of SFRP-Wnt interactions and discuss the new and emerging roles of SFRPs.

Palabras clave

Bmp; signalling antagonists; cancer; diseases

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