A FAMILY OF SECRETED PROTEINS CONTAINS HOMOLOGY TO THE CYSTEINE-RICH LIGAND-BINDING DOMAIN OF FRIZZLED RECEPTORS

This paper describes the identification of a new family of mammalian g enes that encode secreted proteins containing homology to the cysteine -rich ligand-binding domain found in the frizzled family of transmembr ane receptors, The secreted frizzled-related proteins (sFRPs) are appr oximately 30 kDa in size, and each contains a putative signal sequence , a frizzled-like cysteine-rich domain, and a conserved hydrophilic ca rboxy-terminal domain, The sFRPs are not the products of differential splicing of the known frizzled genes, Glycosylphosphatidylinositol-anc hored derivatives of sFRP-2 and sFRP-3 produced in transfected human e mbryonic kidney cells confer cell-surface binding by the Drosophila Wi ngless protein, These observations suggest that sFRPs may function in vivo to modulate Wnt signaling, or, alternatively, as novel ligands fo r as yet unidentified receptors.