Recombinant Human FGF-8f Protein

FGF-8, a member of the fibroblast growth factor family, is a secreted heparin-binding protein that was originally discovered as a growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells (1-3). Alternative splicing of mouse FGF-8 mRNA generates eight secreted isoforms, designated a-h, but only FGF-8a, b, e and f exist in humans (4). FGF-8 contains a 22 amino acid (aa) signal sequence, an N-terminal domain that varies according to the isoform (84 aa for FGF-8f, the longest form in humans; 20 aa for the shortest, FGF-8a), a 125 aa FGF domain and a 37 aa proline-rich C-terminal sequence. The FGF domain of FGF-8 shares the most aa identity with FGF-17 (75%) and FGF-18 (67%), and these three form an FGF subfamily (2). Human and mouse FGF-8f share 98% aa identity (4), while the human FGF-8a sequence, which is common to all isoforms, shares 100% aa identity with mouse, rat and bovine FGF-8a, and 99%, 83%, 83% and 78% aa identity with canine, Xenopus, chicken and zebrafish FGF-8a, respectively. FGF-8 is widely expressed during embryogenesis, and mediates epithelial-mesenchymal transition. It plays an organizing and inducing role during gastrulation, and regulates patterning of the midbrain/hindbrain, eye, ear, limbs and heart in the embryo (2, 5-8). The isoforms may play different roles in development. FGF-8a, b and e have transforming activities, although FGF-8b shows the strongest receptor affinity and oncogenic capacity (1, 5, 9, 10). FGF-8 shows limited expression in the normal adult, but low levels are found in the reproductive and genitourinary tract, peripheral leukocytes and bone marrow hematopoietic cells (3, 9, 11).