Secreted Frizzled Related Proteins (sFRPs) are a family of secreted, soluble vertebrate glycoproteins which contain homology to the Wnt-binding domain of the Frizzled (Fz) family of transmembrane receptors. sFRPs are approximately 30-35 kDa in size and are comprised of 3 domains: a signal sequence; an N-terminal Fz cysteine-rich domain (CRD) with 10 conserved cysteines; and a C-terminal heparin-binding region with weak homology to Netrin. The Fz CRD mediates Wnt-binding and is present in all Fz and sFRP family members (1).
sFRP-1, also known as secreted apoptosis-related protein 2 (SARP-2), FRP and FrzA, is expressed in the embryonic kidney, eye, brain, teeth, salivary gland and small intestine, most often at sites of epithelial-mesenchyme interaction (5). Expression in the adult animal is strong in the eye, kidney, and heart and also prevalent in the brain and lung (2, 5). sFRP-1 was first characterized as a protein that enhances the sensitivity of cells to apoptotic stimuli (3) and as an antagonist of Wnt signaling in Xenopus embryos (4). It is also characterized as a tumor suppressor in breast (6) and cervical carcinomas (7). In contrast, sFRP-1 is expressed by the majority of malignant gliomas (8) and contributes to the development of uterine leiomyomas (9), suggesting that the role of sFRP-1 is dependent on cell context. sFRP-1 has diverse activities, from inducing angiogenesis (10) in a variety of in vivo models to helping regulate Wnt-4 signaling (with sFRP-2) in renal organogenesis (11). Mouse and human sFRP-1 proteins share 94% amino acid identity (1).
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