Recombinant Mouse FGF-21 Protein

Fibroblast growth factor 21 (FGF-21) is a member of the FGF gene family. Based on its structure, FGF-21 is further classified into a subfamily of FGFs along with FGF-19 and -23 (1). Mouse FGF-21 is a 210 amino acid (aa) polypeptide that contains a 120 aa core FGF domain and a hydrophobic N-terminus signal sequence. The signal sequence is cleaved to release the soluble 180 aa mature FGF-21 protein (2). At the amino acid sequence level, mature mouse FGF-21 is 81% and 92% identical to mature human and rat FGF-21, respectively. In comparison to other FGF subfamilies, a heparin-binding domain is uniquely absent in FGF-19 subfamily members. Lack of this domain confers endocrine function to FGF-19 members and enables them to freely diffuse within tissues and accumulate in the circulatory system (3, 4). The biological activity of FGF-21 requires binding to Klotho  beta, a co-receptor that is in complex with cell surface FGF receptors (FGF R) (5, 6). Binding of FGF-21 to Klotho  beta facilitates FGF R activation and autophosphorylation resulting in the initiation of multiple downstream signaling cascades (7, 8). FGF-21 cannot independently bind to FGF Rs, thus its effects are restricted to target tissues that express Klotho  beta. FGF-21 functions as a physiological regulator of cellular metabolism, including glucose uptake in adipocytes and cellular sensitivity to insulin. FGF-21 is basally expressed in the pancreas, thymus, and liver, as well as in adipose tissue (3, 9). Local and systemic metabolic stress has been shown to induce expression of FGF-21 in the liver, muscles, and fat (10-12). Modulation of FGF-21 expression is associated with a number of metabolic disorders, including obesity and diabetes (7, 13). FGF-21 is also involved in promoting cell survival and proliferation, modulating mesenchymal stem cell differentiation, regulating circadian rhythm, and controlling reproductive capacity during nutrient deprivation (14-18).