Secreted Frizzled Related Proteins (sFRPs) are a family of vertebrate proteins which contain homology to the ligand-binding domain of the Frizzled family of transmembrane receptors. sFRPs are approximately 30-35 kDa in size and are comprised of 3 domains: a signal sequence; a cysteine-rich domain (CRD) of about 110 amino acids (aa) with high degree of similarity to the Frizzled proteins, including 10 conserved cysteines; and a 175 aa conserved hydrophilic carboxy terminal region. Because sFRPs contain a CRD very similar to the region responsible for binding Wnt ligands in Frizzleds, sFRPs are thought to act as soluble antagonists of Wnt signals, often postulated to act as tumor suppressor genes (1).
sFRP-4, also known as DDC-4, FrpAP, frpHE and FrzB-2, is expressed in brain, kidney, lung, ovary, prostate, mammary gland, and endometrium (1, 2). This protein shows complex functions with respect to cell survival: it is up‑regulated with apoptosis during ovulation (3), regulates apoptosis in chondrocytes (4), and promotes apoptosis in mammary glands when expressed in transgenic mice (5). On the other hand, sFRP-4 can also act to enhance growth as it is up‑regulated in endometrial and breast carcinomas (6, 7). Since it is not detected in other carcinomas such as the ovary, colon, and pancreas, this suggest that its role in cancer is likely to be tissue dependent (6). In addition sFRP-4 is characterized as a circulating phosphaturic factor expressed by tumors associated with osteomalacia that antagonizes renal Wnt signaling (7). Of all the secreted frizzled related proteins, sFRP-4 is most closely related to sFRP-3 (1). Mouse and human sFRP-4 proteins share 92% aa identity.
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