Recombinant Human Follistatin 288 (FS-288) Protein

Follistatin 288 (FST288) is one of three forms of follistatin, a secreted glycoprotein that was first identified as a follicle-stimulating hormone inhibiting substance in ovarian follicular fluid (1, 2). Human follistatin 288 cDNA encodes a 317 amino acid (aa) protein with a 29 aa signal sequence, and a 288 aa mature region. Human FST288 shares 97 - 99% aa identity with corresponding regions of mouse, rat, equine, ovine, porcine and bovine FST. All forms of follistatin, including FST288, FST303 and FST315, contain an N-terminal atypical TGF binding domain and three follistatin domains (FS1 - 3) that contain EGF-like and kazal-like motifs. A highly acidic C-terminal tail is missing in the splice variant FST288, partially present in the proteolytically produced FST303, and full-length in the most abundant form, FST315 (5, 8, 9). FSTs inhibit activins by surrounding activin dimers. FST288 shows the highest affinity for activins due to its extended configuration, while FST315 is in a folded form (2, 8). Expression of the isoforms is restricted such that FST288, which has higher affinity for heparin-sulfated proteoglycans when unbound, is present in tissues while FST315 is the sole form in plasma and ovarian follicular fluid (5, 8, 9). In addition to activin, follistatins regulate the bioavailability of other members of the TGF-beta superfamily, such as BMP6, BMP7 and myostatin (5). Follistatins also regulate hematopoietic stem cell adhesion to fibronectin via FS2, and bind angiogenin via FS2 and FS3 (6, 7). Genetic deletion of follistatin in mice, or expression of only the FST288 form, is perinatally lethal due to defects of lung, skin and musculoskeletal system (10). Mice that express only the FST315 isoform survive, but exhibit defects in vascularization and female fertility (10).