Recombinant Human GASP-1/WFIKKN2 Protein

Growth and differentiation factor-associated serum protein-1 (GASP-1) was isolated in a screen to identify proteins in mice that copurify with myostatin (GDF-8), a potent negative regulator of skeletal muscle mass (1). The GASP-1 cDNA encodes a 571 amino acid protein that contains a 29 amino acid signal sequence and is comprised of many conserved domains: WAP, Follistatin/Kazal, Immunoglobulin, two tandem Kunitz, and Netrin (1). Two related human proteins which contain the same domain structure are called WFIKKN (based on the presence and order of these conserved domains) and WFIKKNRP (WFIKKN-related protein) (2). Mouse GASP-1 is homologous to human WFIKKN2, also know as WFIKKNRP and mouse GASP-2 to human WFIKKN. Human GASP-1 is the same protein as WFIKKN2. WAP, Follistatin, Kazal and Netrin domains are all implicated in protease inhibition, and these proteins may be multivalent protease inhibitors (3). GASP-1 and -2 show distinct expression patterns both in the developing fetus and the adult. In the developing fetus, GASP-1 expression is highest in the brain, skeletal muscle, thymus and kidney while GASP-2 is abundant in the lung, skeletal muscle and liver (4). In the adult, GASP-1 is primarily expressed in the ovary, testis, and brain while GASP-2 is in the pancreas, liver, and thymus (4). GASP-1 inhibits myostatin and the highly related protein, GDF-11, but not Activin or TGF-beta in vitro (1). In addition, GASP-1 binds directly but independently to both mature myostatin and the myostatin propeptide (1). By amino acid sequence, human GASP-1 is 90% and 55% identical to mouse GASP-1 and human GASP-2, respectively.