βKlotho is required for metabolic activity of fibroblast growth factor 21
| Autor: | Makoto Kuro-o, Yasushi Ogawa, Hiroshi Kurosu, Regina Goetz, Masaya Yamamoto, Anna V. Eliseenkova, Kevin P. Rosenblatt, Moosa Mohammadi, Animesh Nandi |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
FGF21 Glucose uptake Biology Fibroblast growth factor Cell Line Mice chemistry.chemical_compound Internal medicine Adipocyte Adipocytes medicine Animals Humans Receptor Klotho Proteins Multidisciplinary Membrane Proteins Biological Sciences Receptors Fibroblast Growth Factor Fibroblast Growth Factors Endocrinology Gene Expression Regulation chemistry Mitogen-activated protein kinase biology.protein Phosphorylation Signal transduction Protein Binding Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 104:7432-7437 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0701600104 |
| Popis: | Fibroblast growth factor 21 (FGF21) is a liver-derived endocrine factor that stimulates glucose uptake in adipocytes. Here, we show that FGF21 activity depends on βKlotho, a single-pass transmembrane protein whose expression is induced during differentiation from preadipocytes to adipocytes. βKlotho physically interacts with FGF receptors 1c and 4, thereby increasing the ability of these FGF receptors to bind FGF21 and activate the MAP kinase cascade. Knockdown of βKlotho expression by siRNA in adipocytes diminishes glucose uptake induced by FGF21. Importantly, administration of FGF21 into mice induces MAP kinase phosphorylation in white adipose tissue and not in tissues without βKlotho expression. Thus, βKlotho functions as a cofactor essential for FGF21 activity. |
| Databáze: | OpenAIRE |
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