Frzb-1 Is a Secreted Antagonist of Wnt Signaling Expressed in the Spemann Organizer

Abstract

Frzb-1 is a secreted protein containing a domain similar to the putative Wnt-binding region of the frizzled family of transmembrane receptors. Frzb-1 is widely expressed in adult mammalian tissues. In the Xenopus gastrula, it is expressed and regulated as a typical Spemann organizer component. Injection of frzb-1 mRNA blocks expression of XMyoD mRNA and leads to embryos with enlarged heads and shortened trunks. Frzb-1 antagonizes the effects of Xwnt-8 ectopic expression in a non-cell-autonomous manner. Cultured cells transfected with a membrane-tethered form of Wnt-1 bind epitope-tagged Frzb-1 in the 10(-10) M range. The results strengthen the view that the Spemann organizer is a source of secreted inhibitory factors.

Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action

“…While this manuscript was being reviewed, two groups reported that FRZB was a secreted antagonist of Wnt signaling expressed in the Spemann organizer (51,52).…”

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

“…Wnt proteins are believed to induce an intracellular signalling cascade upon binding to the Frizzled receptors. However, this signaling pathway can be modulated by a recently identi®ed group of soluble proteins, the soluble Frizzled-related proteins (sFRPs; secreted apoptosis-related proteins, SARPs) Leyns et al, 1997;Rattner et al, 1997;Finch et al, 1997;Melkonyan et al, 1997). These proteins interfere with Wnt signaling presumably by binding to Wnt proteins, or, alternatively, directly by binding to Frizzled receptors (Ba®co et al, 1999).…”

Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women

“…The potential role of the Wnt signaling pathway in the development of OA has been suggested by the increase in susceptibility for hip OA in women that is associated with 2 functional genetic variants in FRZB, which encodes Frizzled-related protein (FRP) (5)(6)(7)(8). Secreted FRP (sFRP) is a naturally occurring soluble antagonist that competitively binds Wnt to antagonize its ability to signal through Frizzled receptors (9,10). FRP is expressed in adult human cartilage, and its messenger RNA expression is altered in response to cartilage injury in vitro and in vivo (8,11), suggesting that FRP might protect against the development or progression of OA.…”