|Cell Proliferation Induced by FGF-21 and Neutralization by Human FGF-21 Antibody. In the presence of Recombinant Mouse Klotho beta (Catalog # 2619-KB), Recombinant Human FGF-21 (Catalog # 2539-FG) stimulates proliferation in the BaF3 mouse pro-B cell line transfected with human FGF-RIIIc in a dose-dependent manner (orange line). Under these conditions, proliferation elicited by Recombinant Human FGF-21 (500 ng/mL) is neutralized (green line) by increasing concentrations of Goat Anti-Human FGF-21 Mononclonal Antibody (MAB25373). The ND50 is typically 0.5-3 μg/mL.|
Fibroblast growth factor 21 (FGF-21) is a member of the FGF gene family, which currently contains 22 human members. Based on its structure, it is further classified as an FGF19 subfamily member. This subfamily includes FGF-19, -21, and -23. Like all other FGF subfamilies, FGF-19 subfamily members contain a 120 amino acid (aa) core FGF domain that exhibits a beta -trefoil structure (1, 2). Unlike other FGF subfamilies, FGF-19 subfamily members apparently exhibit poor binding to ECM, resulting in highly diffusible molecules (3). The c-DNA for FGF-21 predicts a 209 aa polypeptide that contains a 28 aa signal sequence and a 181 aa mature region (4). Notably, FGF-21, as well as FGF-19 show limited binding to heparin (4). One potential alternate splice form has been reported. It shows a 43 aa substitution for the
C-terminal 12 aa of the standard form (5). Mature human FGF-21 shows 81% aa identity to mouse FGF-21, and is known to be active on mouse cells (4, 6).
The FGF-19 subfamily is considered endocrine in nature. All three subfamily members impact some aspect of metabolism, all three are induced by a nuclear receptor heterodimer that includes RXR, and all three utilize Klotho family members for signal transduction (7, 8, 9). FGF-21 is produced by hepatocytes in response to free fatty acid (FFA) stimulation of a PPARa/RXR dimeric complex (3, 7, 10, 11). This situation occurs clinically during starvation, or following the ingestion of a
high-fat/low-carbohydrate diet. Upon FGF-21 secretion, white adipose tissue is induced to release FFAs from triglyceride stores. Once FFAs reach hepatocytes, they are oxidized and reduced to acetyl-CoA. The acetyl-CoA is recombined into 4-carbon ketone bodies (acetoacetate and beta -hydroxybutyrate), released, and transported to peripheral tissues for TCA processing and energy generation (11, 12).
The document you requested is not available online. Please enter the Catalog Number and Lot Number below to have a document emailed to you at the address provided