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Genetic polymorphism in extracellular regulators of Wnt signaling pathway.

Sharma G, Sharma AR, Seo EM, Nam JS - Biomed Res Int (2015)

Bottom Line: Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway.The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex.Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

View Article: PubMed Central - PubMed

Affiliation: Institute for Skeletal Aging & Orthopaedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, Gangwon-do 200-704, Republic of Korea ; Amity Institute of Nanotechnology, Amity University Uttar Pradesh, Noida, Uttar Pradesh 201313, India.

ABSTRACT
The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

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Role of antagonists in Wnt signaling pathway.
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fig2: Role of antagonists in Wnt signaling pathway.

Mentions: Various natural inhibitors of Wnt signaling pathway have been identified till date, which can antagonize or regulate Wnt signaling pathway (Figure 2). The mechanism of Wnt antagonists has been highlighted by various developmental studies performed in various chick and Xenopus models [7, 8]. Broadly, antagonists of Wnt signaling pathway are divided into two classes depending on their functional mechanism, that is, secreted frizzled-related proteins (sFRPs) and Dickkopfs (DKKs). The members of sFRP class can bind to Wnts and thus regulate the association of Wnt ligands to their transmembrane receptors, inhibiting both canonical and noncanonical signaling pathways. The sFRP class constitutes sFRP family proteins: WIF-1 and Cerberus. Another class of antagonists, that is, DKK class, binds to LRP5/LRP6 component of the Wnt receptor complex to inhibit canonical Wnt signaling and constitutes DKK family proteins and sclerostin [9]. Besides antagonists, Wnt signaling pathway is also activated and regulated by some secreted proteins acting as agonists, for example, R-spondin (Rspo) [10].


Genetic polymorphism in extracellular regulators of Wnt signaling pathway.

Sharma G, Sharma AR, Seo EM, Nam JS - Biomed Res Int (2015)

Role of antagonists in Wnt signaling pathway.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402192&req=5

fig2: Role of antagonists in Wnt signaling pathway.
Mentions: Various natural inhibitors of Wnt signaling pathway have been identified till date, which can antagonize or regulate Wnt signaling pathway (Figure 2). The mechanism of Wnt antagonists has been highlighted by various developmental studies performed in various chick and Xenopus models [7, 8]. Broadly, antagonists of Wnt signaling pathway are divided into two classes depending on their functional mechanism, that is, secreted frizzled-related proteins (sFRPs) and Dickkopfs (DKKs). The members of sFRP class can bind to Wnts and thus regulate the association of Wnt ligands to their transmembrane receptors, inhibiting both canonical and noncanonical signaling pathways. The sFRP class constitutes sFRP family proteins: WIF-1 and Cerberus. Another class of antagonists, that is, DKK class, binds to LRP5/LRP6 component of the Wnt receptor complex to inhibit canonical Wnt signaling and constitutes DKK family proteins and sclerostin [9]. Besides antagonists, Wnt signaling pathway is also activated and regulated by some secreted proteins acting as agonists, for example, R-spondin (Rspo) [10].

Bottom Line: Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway.The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex.Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

View Article: PubMed Central - PubMed

Affiliation: Institute for Skeletal Aging & Orthopaedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, Gangwon-do 200-704, Republic of Korea ; Amity Institute of Nanotechnology, Amity University Uttar Pradesh, Noida, Uttar Pradesh 201313, India.

ABSTRACT
The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

Show MeSH