Secreted Frizzled-related Protein 1 - Function

Function

Secreted frizzled-related protein 1 (SFRP1) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. SFRP1 and SFRP5 may be involved in determining the polarity of photoreceptor cells in the retina. SFRP1 is expressed in several human tissues, with the highest levels in heart.

The Secreted frizzled-related protein (SFRP) family consists of five secreted glycoproteins in humans (SFRP1, SFRP2, SFRP3, SFRP4, SFRP5) that act as extracellular signaling ligands. Each SFRP is ~300 amino acids in length and contains a cysteine-rich domain (CRD) that shares 30-50% sequence homology with the CRD of Frizzled (Fz) receptors. SFRPs are able to bind Wnt proteins and Fz receptors in the extracellular compartment. The interaction between SFRPs and Wnt proteins prevents the latter from binding the Fz receptors. SFRPs are also able to downregulate Wnt signaling by the formation of an inhibitory complex with the Frizzled receptors. The Wnt pathway plays a key role in embryonic development, cell differentiation and cell proliferation. It has been shown that the deregulation of this critical developmental pathway occurs in several human tumor entities.

SFRP1 is a 35 kDa prototypical member of the SFRP family. It acts as a biphasic modulator of Wnt signaling, counteracting Wnt-induced effects at high concentrations and promoting them at lower concentrations. It is located in a chromosomal region (8p12-p11.1) that is frequently deleted in breast cancer and is thought to harbour a tumor suppressor gene.