Description
Growth differentiation Factor 8 (GDF-8), also known as myostatin, is a secreted protein that is expressed specifically in developing and adult skeletal muscle. It controls myoblast proliferation and is a potent negative regulator of skeletal muscle mass.GDF-8 belongs to the transforming growth factor β (TGF-β) superfamily, which includes the TGF-βs, bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), activins, inhibins, leftys, nodal, Mullerian inhibitory substance (MIS) and the glial cell line-derived neurotrophic factors (GDNFs).2 All TGF-β superfamily members are synthesized and secreted as a homodimeric prepropeptide that is cleaved by proprotein convertases such as furin to generate the dimeric N- terminal propeptide and the dimeric C-terminal mature active protein. The C- terminal mature protein contains the characteristic conserved cysteine residues involved in the formation of the cysteine knot domain. Mouse GDF-8 cDNA encodes a 376 amino acid residue (aa) preproprotein with a putative 24 aa signal peptide, a 243 aa propeptide and a 109 aa mature protein.1 As is the case with most TGF-β family proteins, GDF-8 is highly conserved across species. Mature human, mouse, rat, and cow GDF-8 share 100% aa sequence identity. Among TGF-β family members, GDF-8 is most closely related to GDF- 11/BMP-11. The two proteins share 65% overall aa sequence, within their mature regions, the two proteins differ only by 11 aa.residues. Similarly to TGF-β1, 2, and 3, the GDF-8 homodimeric propeptide and mature protein remained non- covalently linked after proteolytic cleavage, and is released as a biologically inactive latent complex that does bind its receptor.3 In serum, GDF-8 has also been found to exist in a large latent complex that also included FLGR (follistatin-related gene) and GASP-1 (growth and differentiation factor- associated serum protein-1) in addition to the propeptide.4 R&D Systems' recombinant GDF-8 propeptide is capable of associating with the active GDF-8 with high- affinity to reconstitute the latent complex and is potent GDF-8 antagonist