Recombinant Human Follistatin (aa 30-344) Protein

Follistatin (FST) is a secreted glycoprotein that was first identified as a follicle-stimulating hormone inhibiting substance in ovarian follicular fluid (1, 2). Human Follistatin cDNA encodes a 344 amino acid (aa) protein with a 29 aa signal sequence, an N-terminal atypical TGF binding domain, three Follistatin domains that contain EGF-like and kazal-like motifs, and a highly acidic C-terminal tail. The first Follistatin domain (FS1) contains a heparin binding site, while FS1 and FS2 are most critical for activin binding and neutralization (3, 4). In addition to activin, Follistatin regulates bioavailability of many non-TGF-beta members of the TGF-beta superfamily, such as BMP6, BMP7 and myostatin (5). It also regulates hematopoietic stem cell adhesion to fibronectin via FS2, and binds angiogenin via FS2 and FS3 (6, 7). Some Follistatin binding partners will also bind Follistatin-like proteins such as FSL-3 (3, 5, 6). Of three Follistatin isoforms, the full-length mature Follistatin (FST315) is the most abundant and the sole form in plasma, but has lower binding affinity for both activins and heparins than alternative isoforms (5, 8, 9). The acidic tail is missing in the splice variant FST288 which shows the highest affinity for activins, while a partial tail exists in the proteolytically produced FST303, which shows intermediate activin affinity (5, 8, 9). FST315 shares 98% aa identity with mouse, rat, equine and ovine FST, 99% with porcine and 97% with bovine FST. 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). Expression of only the FST315 isoform allows survival, with defects in vascularization and female fertility (10).