βKlotho is required for metabolic activity of fibroblast growth factor 21
βKlotho is required for metabolic activity of fibroblast growth factor 21
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DOI：
10.1073/pnas.0701600104
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发表时间：
2007-05-01
影响因子：
11.1
通讯作者：
Kuro-o, Makoto
中科院分区：
文献类型：
--
作者：
Ogawa, Yasushi;Kurosu, Hiroshi;Kuro-o, Makoto
成纤维细胞生长因子21（FGF21）是肝源性内分泌因子，其刺激脂肪细胞中的葡萄糖摄取。在这里，我们表明，FGF 21的活性取决于β Klotho，一个单程跨膜蛋白，其表达诱导分化过程中从前脂肪细胞脂肪细胞。β Klotho与FGF受体1c和4发生物理相互作用，从而增加这些FGF受体结合FGF 21并激活MAP激酶级联的能力。在脂肪细胞中通过siRNA敲低β Klotho表达减少了FGF 21诱导的葡萄糖摄取。重要的是，向小鼠施用FGF 21诱导了白色脂肪组织中的MAP激酶磷酸化，而不是在没有β Klotho表达的组织中。因此，β Klotho作为FGF 21活性所必需的辅因子发挥作用。
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 beta Klotho, a single-pass transmembrane protein whose expression is induced during differentiation from preadipocytes to adipocytes. beta Klotho 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 beta Klotho 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 beta Klotho expression. Thus, beta Klotho functions as a cofactor essential for FGF21 activity.