Recombinant Human Frizzled-1 Fc Chimera Protein, CF

Frizzled-1 is one of at least ten seven-transmembrane (7TM) glycoproteins of the Frizzled family of Wnt receptors (1 - 3). Frizzled proteins are thought to be G-protein-coupled (1, 4). Wnt engagement, with low density lipoprotein receptor-related proteins LRP-5 or LRP-6 acting as co-receptors, stabilizes beta -catenin and promotes gene transcription that is important in development and tissue maintenance (1). Frizzled-1 can also act as a Wnt antagonist, for example, when sequestered from LRP-5/6 by LRP-1 (5, 6). Human Frizzled-1 cDNA encodes 647 aa including a 69 aa signal peptide, an extracellular cysteine-rich domain (CRD, aa 111 - 230) that binds Wnts and is highly conserved among Frizzleds, a linker region, the 7TM region, and the C-terminal cytoplasmic domain (2). Most Frizzleds, including Frizzled-1, contain a C-terminal PDZ binding motif (1). Within aa 73 - 253, human Frizzled-1 shares 94%, 93%, 97% and 98% aa identity with mouse, rat, bovine and canine Frizzled-1, respectively. Frizzleds can form homodimers or selective hetero-oligomers with other family members, which can involve the TM regions and possibly the CRD (1, 7). Frizzled-1 shares high aa identity (~76%) with Frizzled-2 and -7, but may differ in expression and Wnt selectivity (3, 8). Specifically, Wnt-3a interaction with rat Frizzled-1, but not Frizzled-2, blocks toxicity of the Alzheimers A beta peptide on PC12 cells (8). In bone, Frizzled-1 may be part of a feedback mechanism to modulate the effects of BMP-2 on mesenchymal cells (6, 9). Frizzled-1 is also one of the purported Wnt10b receptors whose signaling inhibits adipocyte differentiation (10). It is widely expressed, with mRNA detection in adult heart, placenta, lung, kidney, pancreas, prostate, and ovary, and in fetal lung and kidney (2).