GDF8 Signaling Domain (human, recombinant)

Growth differentiation factor 8 (GDF8) is a myokine and member of the TGF-β superfamily.^1,2 It is produced in skeletal and cardiac muscle cells as a proprotein, which shares sequence identity between the human, mouse, and rat.^1,3 The proprotein is cleaved in the endoplasmic reticulum into a protein containing a prodomain and C-terminal signaling domain.^1,4,3 This protein is secreted and forms homodimers that either circulate or remain near the extracellular membrane in a latent state.⁵ The prodomain is cleaved by bone morphogenetic protein 1 (BMP1) or tolloid family metalloproteinases, releasing the signaling domain to activate TGF-β receptor type 2 (TGFBR2) and negatively regulate muscle growth and differentiation.^5,1,2 Knockout of Myst, the gene expressing Gdf8, increases muscle mass, muscle fiber length, bone mineral content (BMC), and bone size in Myst^-/- mice compared to wild-type mice.⁶ The levels of full-length GDF8 and GDF8 prodomain are increased in left ventricle tissue samples from patients with dilated- or ischemic cardiomyopathy.³ Cayman's GDF8 Signaling Domain (human, recombinant) protein is a disulfide-linked homodimer. The reduced monomer, composed of GDF8 (amino acids 267-375) fused to human IgG1 Fc at its N-terminus, consists of 369 amino acids and has a calculated molecular weight of 40.8 kDa. This protein consists of 108 amino acids and has a predicted N-terminus of Gly20 after signal peptide cleavage. As a result of glycosylation, the monomer migrates to approximately 45 kDa by SDS-PAGE under reducing conditions.

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1. Esposito, P., Picciotto, D., Battaglia, Y., et al. Myostatin: Basic biology to clinical application. Adv. Clin. Chem. 106, 181-234 (2022).

2. McPherron, A.C., Lawler, A.M., and Lee, S.J. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387(6628), 83-90 (1997).

3. George, I., Bish, L.T., Kamalakkannan, G., et al. Myostatin activation in patients with advanced heart failure and after mechanical unloading. Eur. J. Heart Fail. 12(5), 444-453 (2010).

4. Sharma, M., Kambadur, R., Matthews, K.G., et al. Myostatin, a transforming growth factor-beta superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct. J. Cell Physiol. 180(1), 1-9 (1999).

5. Wolfman, N.M., McPherron, A.C., Pappano, W.N., et al. Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases. Proc. Natl. Acad. Sci. USA 100(26), 15842-15846 (2003).

6. Elkasrawy, M.N., and Hamrick, M.W. Myostatin (GDF-8) as a key factor linking muscle mass and skeletal form. J. Musculoskelet. Neuronal. Interact. 10(1), 56-63 (2010).